جستجوی مقالات مرتبط با کلیدواژه « رت » در نشریات گروه « پزشکی »

 Nowadays, some aspects of neuroendocrine and immune systems intercalation are already known. Accordingly, it has been shown that certain immune cells, such as monocytes, can produce and store dopamine in their secretory vesicles. This study was conducted to investigate the effects of dopamine on some immunological functions of the rat peripheral blood monocytes.

 In this experimental study, peripheral blood mononuclear cells of rats were isolated by a ficoll-hypaque gradient. Afterward, the plastic adherent fractions were used as monocytes. Monocytes in the treatment group cocultured for 24 h with 5×10-7 M dopamine, and then their phagocytosis performance, respiratory burst, killing ability, nitric oxide production, neutral red harvest, vital ability, and NF-κB gene expression were investigated.

The results of this study showed that both control or treatment monocytes showed no significant difference in phagocytosis after the challenge with opsonized yeast. Nevertheless, the neutral red uptake, respiratory burst, and nitric oxide production after the challenge with opsonized yeast, and also the expression of NF-κB, were decreased in dopamine-treated monocytes compared to monocytes in the control group (P<0.05). The monocyte vitality of the treatment group did not show any significant effects compared to the monocytes of the control group.

It seems that dopamine dynamically creates an anti-inflammatory phenotype in the monocyte. Therefore, alongside a decrease in the lysosomal compartment activity, the monocytes produce lower levels of free oxygen and nitrogen radicals.

Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and infertility disorder characterized by symptoms such as insulin resistance, hyperandrogenism, anovulation, and ovarian cysts. This study aimed to examine the effect of intraovarian injection of platelet-rich plasma (PRP) on ovarian morphology and insulin resistance in a PCOS rat model.

In this experimental study, 20 Wistar rats were divided into four groups (N=5): control, sham, PCOS, and PCOS group treated with PRP. PCOS was induced using 1 mg/kg of letrozole dissolved in 0.5% carboxymethyl cellulose. The PRP group received 35 microliters of PRP injected directly into both ovaries. After 14 days of treatment, serum insulin levels, blood glucose, and the insulin resistance index (HOMA-IR) were measured. Ovarian tissue sections were also examined for histopathological changes and follicle count.

Intraovarian injection of PRP led to a significant decrease in serum insulin levels (P<0.01) and glucose levels (P<0.01) compared to the PCOS group. The PRP-treated groups exhibited a significant reduction in the insulin resistance index (HOMA-IR) (P<0.0001). Histological analysis demonstrated that a single dose of PRP improved the ovarian pathological condition, resulting in a significant increase in healthy follicles at all developmental stages and corpus luteum (P<0.0001), along with a significant decrease in cystic follicles (P<0.0001).

Intraovarian PRP injection may ameliorate PCOS symptoms, including ovarian morphology and insulin resistance. However, further studies are necessary to elucidate the underlying mechanisms of PRP's effectiveness.

Chronic immobilization is a type of stress that causes behavioral disorders such as anxiety and memory deficits by inducing oxidative stress and inflammation and changing the level of neurotransmitters in the brain. In this research, we investigated the effect of the hydroalcoholic extract of dried lemon peel (Citrus aurantifolia) on learning, spatial memory, and anxiety-like behavior in adult male rats exposed to chronic immobilization.

To induce immobilization stress, the rats were placed in the restrainer for 6 hours every day for 21 consecutive days. Lemon extract (400 mg/kg) was also treated by gavage to the animals. Spatial learning and memory were assessed using the Morris blue maze, and anxiety was studied using an elevated plus maze.

The lemon extract treatment made the animals exposed to immobilization stress swim more time and distance in the target quarter in the water maze compared with the stress group (P < 0.05). The extract increased the percentage of entry into the open arm (P < 0.01) and the percentage of time spent in the open arm (P < 0.05) of the elevated plus maze in these animals.

Dried lemon peel extract improved learning and spatial memory in animals exposed to chronic immobilization and reduced anxiety-like behavior in them. Dried lemon peel extract probably has a neuroprotective effect.

Hexaflumuron, a benzoylphenylurea insecticide, has nephrotoxic effects in mammals. The use of plant antioxidants to improve and prevent poisoning with insecticides has gained popularity. This study aims to evaluate the effects of silymarin, an herbal antioxidant, in ameliorating the lesions caused by hexaflumuron in rat kidneys.

In this experimental study, 40 rats were randomly divided into five groups (n=8): a control group, a group receiving silymarin (200 mg/kg), treatment group 1 (hexaflumuron at 22 mg/kg and silymarin at 100 mg/kg), treatment group 2 (hexaflumuron at 22 mg/kg and silymarin at 200 mg/kg), and a group receiving hexaflumuron (at 22 mg/kg). The gavage lasted for 28 days. After the gavage period, the blood sample was collected from the rats, and kidney tissue samples were obtained post-euthanasia. Histopathological examination was qualitatively conducted to assess lesion presence.

Silymarin significantly reduced the elevated concentrations of serum urea and creatinine induced by hexaflumuron (P<0.05). The use of silymarin largely mitigated vacuolar degeneration and hyperemia caused by hexaflumuron in the kidneys.

Based on the findings, it can be inferred that silymarin at a dose of 200 mg/kg, as an herbal antioxidant, effectively prevents the adverse changes induced by hexaflumuron in the kidneys.

In this study, we examined the impact of a hydroethanolic extract derived from ajwain and carvone (a compound present in ajwain), on learning, spatial memory, and anxiety levels in adult male rats that were chronically immobilized.

There were 60 rats used in this study, divided into six groups of 10 rats each. To expose stress, 30 rats (in 3 groups including Stress, Stress-Carvone, and Stress-Ajwain groups) were placed in a restrainer for 6 hours every day for 21 consecutive days. Stress-Carvone and Stress-Ajwain groups received carvone (20 mg/kg) and ajwain extract (500 mg/kg) by gavage respectively. Thirty rats were also used in three groups (Control, Carvone, and Ajwain groups). Spatial learning and memory were studied using the Morris water maze, and anxiety was assessed by the elevated-plus maze.

Compared to the control group, chronic immobilization caused the rats to swim a longer time (P < 0.01) and distance (P < 0.05) to reach the hidden platform, and a shorter time and distance to swim in the target quarter (P < 0.05) in the Morris water maze. The percentage of entering the open arm in the elevated plus maze (P < 0.001) and the percentage of time staying in this arm (P < 0.01) were lower than the control group.  The carvone improved the performance of stressed animals in the Morris maze, but the ajwain extract had no effect on the memory deficit of stressed animals. Furthermore, treating ajwain extract and carvone increased the percentage of entry into the open arm and the percentage of time spent in the open arm in animals exposed to stress.

Ajwain extract and carvone reduce anxiety behavior in rats exposed to chronic immobility stress; carvone treatment prevents memory impairment in these animals. It is possible that the extract of ajwain (partially through carvone) is effective in reducing damage caused by stress in the nervous system.

Background &

There is a tendency to increase the risk of dementia in patients with periodontitis, but the opposite, the role of Alzheimer's disease on periodontal disease is still unclear, so in this study, the effect of experimental Alzheimer's disease on periodontal inflammatory cells, collagen fibers and neovascularization was investigated in male rats.

In this experimental study, 16 Wistar male rats (230-250 grams) were randomly divided into 2 groups; control (saline) and streptozotocin 3 mg/kg (bilateral ICV injection, with a volume of 10 μl, in both groups). After 4 weeks of treatment, two groups were tested with the Morris water maze. Then the rats were killed by deep anesthesia and sampling from the papilla around the two central incisor teeth was done. Samples were fixed and the paraffin block was prepared, serial 5-micron slices were made with a microtome. After hematoxylin & eosin staining, the number of inflammatory cells (PMNs, eosinophils, and mast cells), angiogenesis, and fibroblasts were counted using a microscope (400×). Data were analyzed using SPSS 21 software and an independent T-test.

The results showed that Alzheimer's disease causes an increase in periodontal inflammatory cells, collagen fibers and new vessels in the gums of mice, and the difference between these changes between the experimental and control groups was significant in all parameters (p<0.00).

According to these findings, Alzheimer's disease causes or aggravates inflammation and increases the rate of periodontal diseases in rat and may have the same effect in humans.

Maintaining the capacity of mitochondrial biogenesis during aging is considered a key factor to prevent the development of age-related diseases. this study aimed to investigate the effect of 8-weeks of high-intensity interval training (HIIT) and hawthorn extract on the peroxisome proliferator- activated receptor-γ gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) proteins levels in the soleus muscle of aged rats.

Thirty-six aged rats were randomly and equally assigned into control (CON), HIIT, extract or combined (COM, HIIT+ extract) groups. The HIIT protocol consisted of 6 to 9 sets×5-min of running on a treadmill, which was performed 4 minutes at 16 m/min and one minuteat a speed velocity of 25 m/min, 5 times a week for 8 weeks. Over the intervention period, rats in the extract and COM groups received 100 mg/kg per day hawthorn. After the interventions, TFAM and PGC-1α protein expression levels were detected in the soleus muscle using the western blotting method.

There was a significant increase in PGC-1α for all interventions when compared to the CON, although this increase in the COM was significantly higher than the other groups. After 8 weeks , there was a significant increase in TFAM level in extract group compared to CON,also, the training groups had more effects on this marker in comparison to the former intervention (p>0.05).

It seems that, 8-weeks of the HIIT+ intake hawthorn is a more efficient approach in improving mitochondrial oxidative capacity compared to HIIT and extract alone.

Diabetes is a group of metabolic disorders that affect the structure and function of other organs in the body, such as the myocardium, and is referred to as cardiomyopathy. However, due to the role of exercise in preventing and treating diabetes complications, the present study was performed to determine the effect of diabetes and high- intensity interval training (HIIT) on tissue expression of miRNA-1 and miRNA-21 in the left ventricle of diabetic male rats.

In this experimental study, twenty adult Wistar male rats were selected and randomly divided into two groups: diabetic and diabetic with HIIT (T) protocols. Accordingly, the rats underwent the HIIT program on smart electronic tape recorders for eight weeks, five days a week. HIIT training was performed with an intensity of 90-85% of maximum speed 6-12 times for 2 minutes and with 3-minute active rest intervals with an intensity of 30% VO2max. At the end of the study contract, all rats were anesthetized and operated on 48 hours after the last intervention without a painless method to determine changes in miR-1 and miR-21 gene expression by real-time PCR in left ventricular tissue.

The results showed that the quantitative relative expression of miRNA-1 in the HIIT + diabetes group was (0.00005 ± 0.000001) and diabetes control (0.00018 ± 0.000005). The Quantitative relative expression of miRNA-21 in the HIIT + diabetes group was (0.00025 ± 0.000001) and in the diabetes control group (0.00011 ± 0.000016). Eight weeks of HIIT training significantly increased the relative expression of miRNA-21 and decreased the expression of miRNA-1 in diabetic rats (P < 0.05). In contrast, the results showed that after eight weeks of diabetes, the relative expression of miRNA-21 decreased significantly, and the expression of miRNA-1 increased (P < 0.05).

Based on the results of this study, it seems that miRNA-210 can be used as an indicator to assess the adaptations associated with exercise training.

Physical inactivity and high-calorie diets have caused obesity and related metabolic diseases, therefore; The aim of this study was to investigate the effect of obesity induction along with endurance training and diet change on weight changes and lipid profiles of male Wistar rats.

The research method was laboratory type. The research subjects included 25 Wistar rats with an age range of 8 to 12 weeks, which were divided into 5 control and experimental groups by targeted selective sampling according to weight and age conditions. In the first stage, 4 days after the weaning period, the food program was started to fatten the rats. A 5-band treadmill was used for endurance training. The training program of the subjects was 30 minutes per day for 8 weeks at a speed of 8 meters per minute. Dependent t-test and one-way analysis of variance were used to analyze the data.

The results showed that there is no significant difference between the pre-test and post-test of the average weight of the obese group + standard diet + aerobics (p = 0.135) and the obese group + standard diet (p = 0.06). Also, there is no significant difference between HDL averages in any of the groups, but there is a significant difference between LDL averages in the control group and other groups (p<0.001).

It seems that endurance exercise has an effect on weight control when a low-fat diet is included.

Menopause is a process that occurs with the permanent cessation of ovarian function in women and has many complications. This study aimed to investigate the effect of vitamin D with chitosan coating along with six weeks of resistance training on the antioxidant indices of the hippocampal tissue of ovariectomized rats.

24 rats were randomly divided into 4 groups of 6. After ovariectomy, rats were divided into menopausal chitosan-coated vitamin D groups, menopausal exercise group, chitosan-coated vitamin D group and menopausal exercise, and menopausal control group. The training group did resistance training 5 days a week for 6 weeks. 24 hours after the last training session, the hippocampus was separated from the brain and the amounts of succinate dehydrogenase (SOD), malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured by ELISA technique. To compare the groups, one-way ANOVA test was used at the alpha level of 0.05.

SOD values ​​were significantly higher in the chitosan-coated vitamin D exercise group than the chitosan-coated vitamin D and menopausal control groups (P<0.05). TAC in the exercise-vitamin D group with chitosan coating was significantly higher than the exercise groups and the postmenopausal control group (P<0.05). Also, the MDA concentration in the exercise group was significantly higher than the vitamin D group with chitosan coating (P<0.05).

Resistance training prevented the increase of oxidative stress and when resistance training is combined with the simultaneous consumption of vitamin D with chitosan coating, due to the possible agonistic effect, it will have a greater effect in reducing menopausal complications and oxidative stress in postmenopausal women.

Lead (Pb) is a toxic heavy metal which causes adverse health effects on humans and animals. N-acetylcysteine (NAC), as an antioxidant agent, decreases tissue damages and inflammations. The aim of this study was to evaluate the effects of N-acetylcysteine on the expression of IL-10 and TGF-β genes in the lung of rats exposed to Pb.

In this interventional quasi-experimental study, the rats were randomly divided into 5 groups, including 1) control, 2) acute dose of Pb, 3) acute dose of Pb + continuous administration of NAC, 4) chronic dose of Pb, and 5) chronic dose of Pb + continuous administration of NAC. Acute dose of Pb (70 mg/kg) was administrated on the first day of the study. Chronic dose of Pb (2 mg/kg) and Continuous administration of N-acetylcysteine (50 mg/kg) was used every day for 4 weeks. Both N-acetylcysteine and Pb were dissolved in sterile water and administrated to rats orally by gavage. Histopathological analysis was performed by tissues staining with hematoxylin-eosin (H&E). qRT-PCR method and one-Way ANOVA statistical tests with a significant level of P<0.05 were used to evaluate the expression of IL-10 and TGF-β genes.

Pb induced inflammation in acute and chronic doses. qRT-PCR analysis showed a significant decrease in IL-10 and a significant increase in TGF-β expressions. However, administration of NAC with Pb led to a decrease in inflammation by upregulation of IL-10 and downregulation of TGF-β genes in the lungs of rats.

Our results suggest that N-acetylcysteine can protect the lungs against Pb toxicity by reducing inflammation.

 Changes in the antioxidant status and changes in the concentration of inflammatory factors through physical activity and supplements are a vague argument for researchers. The aim of this study was to investigate the effect of eight weeks of resistance training (RT) with royal jelly (RJ) on the oxidative system of hippocampal tissue in rats with Alzheimer's disease (AD) induced by trimethylettin.

A total of 60 adult male rats were randomly divided into six groups: 1) Healthy control; 2) AD control; 3) Sham; 4) RJ; 5) RT; and 6) RT+RJ. The RT groups performed three sessions of RT for eight weeks. The RJ groups received 100mg/kg/day RJ dissolved in normal saline by intraperitoneal injection for eight weeks. qRT-PCR technique was used to evaluate changes in SOD, GPX, CAT gene expression of hippocampal tissue.

The results showed that the expression of SOD gene in either the RT and the RT+RJ groups had a significant increase compared to the healthy controls (p=0.001). GPX gene expression in either the RT and the RT+RJ groups was significantly increased compared to the AD controls as well as healthy controls (p=0.001). There was a significant increase in CAT expression in the RT+RJ group compared to the healthy controls (p=0.015). There was a significant decrease in CAT in the AD controls compared to the healthy controls (p=0.038).

It seems that the combination of exercise intervention with RJ may have more positive and obvious effects on the antioxidant system in rats with AD.

Diabetes is a metabolic disease associated with hypoglycemia, hypolipidemia, and liver dysfunction.The aim of this study was to evaluate the effects of hydroalcoholic extract of black seed and honey (dozin) on liver enzymes (AST, ALT, ALP) in streptozotocin-induced diabetic rats.

70 adult male rats weighing approximately 220-200 g were divided into 7  groups: Control group: did not receive any medication. The sham  group received only solvent.  Experimental group 1 and 2: Animals in this group received 2 and 4 g / kg of hydroalcoholic extract of black seed and honey (dosin), respectively. Experimental group 3 received streptozotocin intraperitoneally as diabetic group : Animals in this group received 70 mg / kg of streptozotocin intraperitoneally, experimental group 4 and 5,  Animals in this group first received streptozotocin and then 2 and 4 g / kg of extracts. Rats  were treated for 21 days and at the end of the experimental period, blood samples were collected and serum levels of liver enzymes (AST, ALT, ALP) were measured.

The results show that the levels of AST and ALP enzymes in experimental groups 5 and 4, respectively, compared with experimental group 3 (diabetic group l) and in experimental groups 1 and 2, compared with control and sham groups, showed a significant decrease at the level of p <0.05. In experimental group 3 (diabetic group), the levels of AST and ALP enzymes showed a significant increase compared to control and sham groups.

This study showed that the hydroalcoholic extract of black seed and honey (dosine) probably improves the destructive effects of diabetes on changes in liver enzymes due to its antioxidant properties.

Asthma is a complex and chronic inflammatory disease that causes numerous changes in the shape and function of the respiratory system, including reversible obstruction and stenosis, severe response, and alteration of the airway model, and other body systems, such as the immune system, the nervous system, and the endocrine system. It also affects the psyche of the patient. Today, due to the side effects of anti-inflammatory drugs, there is a growing desire to use traditional medicine. Bee venom due to the presence of numerous antioxidants and anti-inflammatory factors can prevent the increase of free radicals and is effective in reducing the complications of asthma.

To evaluate bee poison, 32 rats (Wistar) were divided into four groups of control, asthma, and asthma receiving categorized 0/5 mg/kg and 1 mg/kg. To inflict the experimental asthma, rats received injective–inhalation ovalbumin. Along with receiving asthma, the treatment groups received bee poison during 10 days, too. At the end of the experiment, the samples were dissected and their lavage fluid was extracted, the white blood cell counted, and the percentages of monocytes and eosinophils in the lavage fluid of the four groups were determined and compared using SPSS running ANOVA with the significance value set at .

The results showed that the total number of white blood cells, with the mean and standard deviation of 229 ± 34 (P≤0.01), percentage of monocytes with the mean of 1.71 ± 0.18 (P≤0.001), and vasinophils with the mean of 1.63 ± 0.26 (P≤0.01) in asthma samples increased significantly compared with those of the control samples.

According to the results, it seems that, due to its antioxidant and anti-inflammatory properties, bee venom may be effective in the treatment of inflammatory diseases, such as asthma.

The prevalence of diabetes has made necessary changes in lifestyle to prevent its complications. In this study, the effect of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) with staxanthin supplementation on inflammatory biomarkers in the cardiac tissue of diabetic rats was investigated.

In this study, 42 male rats (age six weeks), after induction of type 2 diabetes,were randomly divided into seven groups (six in each group): 1)diabetic control; 2) diabetic Sham; 3) diabetes+supplement; 4) diabetes+HIIT; 5) diabetes+HIIT+supplement; 6) diabetes+MICT; and 7) diabetes+MICT+supplement. The HIIT groups ran with an intensity of 80% VO2max, and MICT groups ran with an intensity of about 65% to 75% VO2max on the treadmill (five sessions per week for eight weeks). The supplement was taken daily at a dose of 3 mg per kg. The cardiac tissue was removed 24h after the last training session (night fasting). Inflammatory biomarkers (IL-1b, IL-6, TNF-α, and CRP) of the cardiac tissue were measured by Western blotting.

After eight weeks of training, inflammatory biomarkers showed a significant decrease compared to the control group (p<0.05), and no significant changes were observed in the supplement group.

Due to the effect of MICT and HIIT in reducing inflammatory biomarkers, it can be used as a therapeutic strategy. It seems that the MICT with supplements may have more effective in these patients, while supplements alone have no effect on inflammatory markers.

Diabetes is a well-known disease that has complications such as retinopathy, nephropathy and gastropathy. This study was designed to investigate the effect of thiamine and lead acetate on the colon of induced-alloxan diabetic rats, the effects of which become obvious in the treatment or reduction of tissue complications caused by diabetes.

In this study 63 rats weighing 200 g were divided into 9 groups:1) Group of diabetes+pb acetate 200 ppm; 2) Group of thiamin+pb acetate 200 ppm; 3) Group of thiamine+pb acetate 1000 ppm; 4) Group of diabetes+thiamine+Pb acetate 1000 ppm; 5) Diabetes group; 6) Group of diabetes+thiamine; 7) Group of diabetes+thiamine+acetate 200 ppm; 8) Group of diabetes+pb acetate 1000 ppm; 9) Control group. After a 20-day period, the samples were removed from abdominal cavity and the slides were prepared by using routine tissue method. Then, the slides were evaluated for the stereological and histomorphometric studies.

Ethical Considerations:

 This study was approved by the Code of Ethics GRN1M1903 at the Faculty of Veterinary Medicine, Shahrekord University, and all methods used in the present study, including facilitation, were conducted in full compliance with the ethical principles of animal restraint.

Mean thickness of mucosa-sub-mucosa showed significantly different in groups 6 and 7 compared to other treatment groups. There was a significant difference in the thickness of the muscle layer between the control and all treatment groups except for groups 2, 6 and 7. There was no significant difference in the mean thickness of advantia layer in groups 1, 7 and 8 with the control group. The results also showed a statistically significant difference in the area of different layers of colon tissue between group 1 and control group.

Based on the results of this study, it seems that thiamine has enhancing effects on muscle layer thickness and adventitia layer thickness. On the other hand, the area of the mucosal layer was not affected by the improving effects of thiamine.

Alopecia by reduction of hair follicles at the wound healing site is a complication of cryosurgery that creates an unpleasant appearance in the scar of healed tissue. The aim of this study was to evaluate the effect of low level laser on preventing necrosis of hair follicles and increasing hair follicles in cryosurgery induced wounds.

Fifty male Wistar rats were randomly divided into 2 main experimental and control groups (with and without low power laser) and 5 subgroups. Histopathological examination of the amount of hair follicle count and angiogenesis at intervals of 3, 7, 14, 21 and 28 days was performed in the laboratory. SPSS software was used for statistical analysis. 

There was no significant difference in the  angiogenesis had significantly index between the main groups on days 14 and 21 (P>0.05), but on days 3, 7 and 28, the experimental group had significantly higher angiogenesis than the control group. Throughout the days, both groups showed a significant increase in angiogenesis (P<0.05), except for the third and seventh days in the control group, and in both groups between the 21st and 28th days (P>0.05). In the comparison of hair follicle index, there was an increase on all days, which was significantly higher in the experimental group than the control group (P<0.05). However, no statistical difference was observed between the third and seventh days (P>0.05).

The use of low-power lasers on cryosurgery induced wounds with scars and alopecia can prevent hair follicles necrosis and subsequent increase in their numbers in rats.

The aim of this study was to investigate the response of ERK1/2 protein and muscular morphological adaptations to a period of resistance training with local blood flow restriction.

Twenty healthy male Wistar rats without clinically evident disease (5 weeks old, 120±7 g weight) were divided into four equal groups: control, control with limited blood flow, resistance training and, resistance training with limited blood flow. The resistance group practiced squats for eight weeks with a frequency of three sessions per week. Blood flow restriction was performed using a cuff with a width of 16 mm and a length of 90 mm. For Immunohistochemical test of ERK1/2 and histological studies, the left quadriceps muscle of the left leg was removed. Data analysis was performed by one-way analysis of variance at a level of α≤0.05.

In the resistance training group, the ERK1/2 expression in the quadriceps muscle increased, while decreased in the groups with limited blood flow  (p<0.05). In both groups of the resistance training (with and without blood flow restriction), quadriceps muscle diameter increased (p<0.05). Also, the number of muscle fibers increased significantly (p<0.05).

resistance training seems to induce ERK1/2, which is consistent with increased skeletal muscle growth. Resistance exercises with limited blood flow may result in more muscle hypertrophy. However, such effects of the interaction between resistance training and blood flow restriction on the expression of ERK1/2 was not observed.