摘要
目的:探讨香椿子总多酚(TSTP)对心肌缺血再灌注损伤(MIRI)大鼠细胞凋亡信号通路的影响。方法:采用左冠脉球囊垫扎术,缺血45 min再灌注6 h制备大鼠MIRI模型,随机分为模型组、TSTP高剂量组(100 mg·kg^(-1))、TSTP低剂量组(50 mg·kg^(-1))、假手术组,于造模术前7 d开始灌胃给药;采用染色法评估心肌梗死情况,FCM法检测细胞凋亡率,ELISA法检测胞浆线粒体细胞色素C(Cyt C)含量,荧光底物法检测心肌半胱氨酸蛋白酶caspase-3、caspase-8、caspase-9、caspase-12活性,RT-qPCR法测定心肌凋亡死亡受体通路指标(Fas和Fas-L)、线粒体通路指标(Bax和Bcl-2)、内质网应激通路指标(GRP78和CHOP)的基因表达。结果:TSTP高、低剂量组明显缩小心肌梗死区面积,与模型组比较差异有统计学意义;与模型组相比,TSTP高、低剂量组可显著降低心肌细胞凋亡率,可显著减少胞浆Cyt C释放量,明显降低胞浆caspase-3、caspase-9和caspase-12活性,可明显下调Bax、GRP78及CHOP基因表达,明显上调Bcl-2基因表达,组间差异均有统计学意义;TSTP对Fas、Fas-L基因表达无显著影响。结论:TSTP预处理对MIRI的心肌保护作用是通过抑制线粒体和内质网应激凋亡通路、减轻心肌细胞凋亡反应等实现的。
OBJECTIVE To evaluate the cardioprotective effects of total polyphenols from Toona sinensis seeds(TSTP)on myocardial ischemia reperfusion injury(MIRI)in rats, basing on the cardiomyocyte apoptotic signal pathway.METHODS Rat modelof MIRI was prepared by coronary artery ligation for 45 min followed by 6 hours reperfusion.Rats were divided at randomin tomodel, TSTP(100 mg·kg^(-1)and 50 mg·kg^(-1),respectively)and sham groups.TSTP was orally administered for 7 days before themodel preparation.After the reperfusion, myocardial infarct size was measured by the NBT staining.The cardiomyocyteapoptosis rate was examined by FCM.Cytochrome C(Cyt C)releasing in cytoplasm was detected by ELISA.The caspase activities in cardiomyocytes were examined by fluorescence method.The mRNA expression of apoptotic factors(Fas, Fas-L,Bcl-2,Bax, GRP78 and CHOP)were determined by RT-qPCR.RESULTS TSTP significantly reduced myocardial infarct size, compared to that of model group.The cardiomyocyte apoptosis rates in TSTP groups were significantly reduced.The intracytoplasmic Cyt C releasing and caspase-3,caspase-9 and caspase-12 activities in TSTP groups were significantly inhibited.The Bcl-2 mRNA expression was evidently elevated and Bax, GRP78 and CHOP mRNA expression were evidently reduced in TSTP groups.TSTP showed no significant influence on the Fas and Fas-L mRNA expression.CONCLUSION TSTP pretreatment shows cardioprotective effect on MIRI,and its mechanism maybe involved in preventing the activation of mitochondrial signal pathway and endoplasmic reticulum stress signal pathway and inhibition of cardiomyocyte apoptosis.
作者
吴国学
李小霞
李茹月
张国斌
WU Guo-xue;LI Xiao-xia;LI Ru-yue;ZHANG Guo-bin(Department of Pharmacy,People's Hospital of He'nan University of Chinese Medicine/People's Hospital of Zhengzhou,He'nan Zhengzhou 450003,China;The Fifth Clinical College of Medicine,He'nan University of Chinese Medicine,He'nan Zhengzhou 450003,China;Pharmacy College,He'nan University of Chinese Medicine,He'nan Zhengzhou 450046,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第2期145-149,共5页
Chinese Journal of Hospital Pharmacy
基金
河南省医学科技攻关计划联合共建项目(编号:2018020834)。
关键词
香椿子
心肌缺血/再灌注损伤
心肌细胞凋亡
凋亡信号通路
Toona sinensis seeds
myocardial ischemiareperfusion injury
cardiomyocyte apoptosis
apoptoticsignal pathway
