摘要
目的基于p38MAPK-CRYAB途径探讨8-O-乙酰山栀子苷甲酸对急性心肌梗死大鼠的影响及作用机制。方法采用结扎冠状动脉左前降支的方法建立急性心肌梗死大鼠模型,取50只造模成功的雄性SD大鼠随机分为模型组、阳性对照组、8-O-乙酰山栀子苷甲酸低、中、高剂量组,每组10只,另选10只作为空白对照组。空白对照组与模型组均给予等体积生理盐水,阳性对照组给予阿司匹林肠溶片100mg/(kg·d),8-O-乙酰山栀子苷甲酸低、中、高剂量组分别给予8-O-乙酰山栀子苷甲酸10、20及30mg/(kg·d),连续给药14天。检测大鼠心功能;HE染色法观察大鼠心肌组织病理变化;TUNEL法检测心肌细胞凋亡;ELISA检测SOD、LDH、GSH-Px和MDA水平;RT-PCR检测Bcl-2、Bax和Caspase-3mRNA表达;Western blot检测p-p38MAPK/p38MAPK和p-CRYAB/CRYAB表达。结果8-O-乙酰山栀子苷甲酸可显著改善急性心肌梗死大鼠的心功能及心肌组织病理变化(P<0.05),降低心肌细胞凋亡率(P<0.05),减轻氧化应激损伤(P<0.05),上调抑凋亡基因Bcl-2表达,下调促凋亡基因Bax和Caspase-3表达(P<0.05),促进p38MAPK和CRYAB磷酸化(P<0.05),但各组间p38MAPK和CRYAB蛋白表达无明显变化(P>0.05)。结论8-O-乙酰山栀子苷甲酸可显著改善急性心肌梗死大鼠心肌损伤症状,上调Bcl-2表达,下调Bax和Caspase-3表达,促进p38MAPK和CRYAB磷酸化,其作用机制可能与p38MAPK-CRYAB途径有关。
Aim To investigate the effect and its mechanism of 8-O-acetyl-SM on acute myocardial infarction rats based on p38 MAPK-CRYAB pathway. Methods A rat model of acute myocardial infarction was established by ligation of the left anterior descending coronary artery. Fifty male SD rats were randomly divided into model control group, positive control group,8-O-acetyl-SM low,medium and high dose groups,with 10 rats in each group. In addition,10 rats were used as blank control groups. The blank control group and the model control group were given the same volume of normal saline,the positive control group was given aspirin enteric-coated tablets ( 100mg /( kg·d) ) ,and the 8-O-acetyl- SM low,medium and high dose groups were given 10,20 and 30 mg /( kg·d) 8-O-acetyl-SM,continuous administration for 14 days. The changes of cardiac function were detected,HE staining was used to observe the pathological changes of myocardium in rats,TUNEL was used to detect the apoptosis of myocardial cells,ELISA was used to detect the levels of SOD,LDH,GSH-Px and MDA,RT-PCR was used to detect the mRNA expression of Bcl-2,Bax and Caspase-3,Western blot was used to detect the expression of p-p38 MAPK/p38 MAPK and p-CRYAB/CRYAB. Results 8-O-acetyl-SM significantly could improve cardiac function and pathological changes of myocardial tissue in rats with acute myocardial infarction ( P<0.05) ,reduce myocardial apoptosis rate ( P<0.05) ,reduce oxidative stress damage ( P<0.05) ,up-regulate the expression of Bcl-2,down-regulate the expression of Bax and Caspase-3 ( P<0.05) ,promote phosphorylation of p38 MAPK and CRYAB ( P<0.05) ,but there was no significant change in the expression of p38 MAPK and CRYAB protein among the groups ( P>0.05) . Conclusion 8-O-acetyl-SM can significantly improve myocardial injury symptoms,upregulate Bcl-2 expression,down-regulate Bax and Caspase-3 expression,promote p38 MAPK and CRYAB phosphorylation, and its mechanism may be related to p38 MAPK-CRYAB pathway.
作者
涂秋英
杨宇龙
胡婕
张艳慧
TU Qiuying;YANG Yulong;HU Jie;ZHANG Yanhui(Department of Cardiology,Jiangxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine,Nanchang, Jiangxi 330003,China;Department of Gastroenterology,the Fourth Affiliated Hospital of Nanchang University, Nanchang,Jiangxi 330003,China)
出处
《中国动脉硬化杂志》
CAS
2018年第12期1245-1251,共7页
Chinese Journal of Arteriosclerosis
