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ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.
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@#Objective To explore initially the role of p38 mitogen activated protein kinases(p38 MAPK) in cerebral ischemic preconditioning.Methods Healthy adult SD rats were randomly divided into 5 groups: normal control group,sham-operated group,ischemia preconditioning or ischemia tolerance group,peripheral noxious control group,peripheral noxious tolerance group.SDS-PAGE,Western blot and Gel Doc imagine systems were applied to determine the p38 MAPK phosphorylation and protein expression in somatosensory cortex and hippocampus of rat.Results No significant changes of p38 MAPK in phosphorylation level and protein expression were found both in somatosensory cortex and hippocampus after ischemia preconditioning(P>0.05,n=6).Conclusion The development of cerebral ischemia preconditioning of rat might be not involved the phosphorylation and protein expression of p38 MAPK.
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AIM: To investigate the effects of fenofibrate(FB) and rosiglitazone(RG) on the signal passway of p38 mitogen-activated protein kinases(p38 MAPK) in glomerular mesangial cells cultivated in high concentration of glucose.METHODS: Rat mesangial cells(MC) were incubated in 5.5 mmol/L normal control glucose,25 mmol/L high glucose(HG),HG+100 ?mol/L fenofibrate(FB+HG),HG+20 ?mol/L rosiglitazone maleate(RG+HG),respectively.The fibronectin(FN) and type Ⅳ collagen(Col-Ⅳ) in supernatant were determined by ELISA.The expressions of p38MAPK and phospho-p38MAPK proteins in cytoplasm and nuclei were detected by Phospho-ELISA.The mRNA expression of p38MAPK was detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).RESULTS: Compared with normal control,the Col-Ⅳand FN in supernatant in HG group were much higher,the expression of p-p38MAPK was increased in cytoplasms and nuclei.Col-Ⅳ and FN were obviously decreased with the treatment of FB or RG,and the expression of p-p38MAPK in nuclei was down-regulated,but the expression of p-p38MAPK in intracytoplasm had no changes.There were no significant differences of the expressions of total protein and mRNA of p38MAPK among four groups.CONCLUSION: FB,RG could inhibit the activation of p38MAPK in nuceli of MC cultivated in high concentration of glucose,and then reduce the synthesis of extracellular matrix.