虫草素预处理减轻SD大鼠心肌缺血再灌注损伤  

Preconditioning with cordycepin attenuates myocardial ischemia-reperfusion injury in SD rats

作　　者：钱国强[1] 张小照 丁晶晶[1] 尹晓峰[1] 

机构地区：[1]黄淮学院医学院,河南驻马店463000

出　　处：《中国病理生理杂志》2017年第3期543-547,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81173189);河南省科技攻关项目;河南省高等学校青年骨干教师培养计划

摘　　要：目的:研究大鼠心肌缺血再灌注(IR)损伤中,虫草素(cordycepin,Cordy)能否通过调节微小RNA-455(miR-455)的表达和减少内质网应激(endoplasmic reticulum stress,ERS)引起的凋亡发挥心肌保护作用。方法:体重250~300 g的SD大鼠随机分为3组:对照(control)组,大鼠只进行开胸手术;IR组,大鼠心肌缺血30 min,再灌注120 min;虫草素治疗组(IR+Cordy组):大鼠缺血再灌注前给予虫草素(10 mg/kg)股静脉注射,每天1次,共注射1周。全自动化学分析法检测大鼠血清中乳酸脱氢酶(LDH)和肌酸激酶同工酶MB(CK-MB)活性。TUNEL试剂盒检测心肌内皮细胞(endothelial cells,EC)凋亡率,电镜观察EC超微结构的改变。RT-q PCR法检测心肌组织miR-455及ERS介导的细胞凋亡信号通路的标志物葡萄糖调节蛋白78(glucose-regulated protein 78,Grp78)和caspase-12的mRNA表达。结果:与control组比较,IR组EC的凋亡率明显升高(P<0.05);与IR组比较,虫草素组EC的凋亡率明显下降(P<0.05)。与control组比较,IR组的EC线粒体肿胀,膜不规整,内皱疏松有空泡,基粒消失,核膜不规整,染色质浓集、边集,核仁消失,甚至出现凋亡小体;IR+Cordy组与IR组比较症状大为改善。与control组比较,IR组心肌组织Grp78和caspase-12的mRNA及miR-455含量均升高(P<0.05);与IR组比较,IR+Cordy组Grp78和caspase-12的mRNA及miR-455的含量均降低(P<0.05)。结论:虫草素可有效减轻心肌IR后大鼠心肌EC凋亡,降低心肌组织miR-455表达,抑制内质网应激。AIM：To study whether cordycepin （Cordy） plays a role in myocardial protection by regulating the expression of microRNA-455 （ miR-455） and reducing apoptosis induced by endoplasmic reticulum stress in the ischemia -reperfusion （IR） rats.METHODS： SD rats （250 -300 g） were randomly divided into 3 groups： control group, the chests of the rats were only opened;IR group, the rats were given myocardial ischemia for 30 min, and then reperfusion for 120 min;IR＋Cordy group：before IR, the rats were given Cordy （10 mg/kg） through femoral vein injection once a day for one week, and the last injection was given 30 min before ischemia.Automated biochemical analysis was used to detect rat serum activity of LDH and CK-MB.The myocardial endothelial cell （ EC） apoptotic rate was measured by TUNEL , and the ultrastructural changes of the myocardial EC were observed under transmission electron microscope .RT-qPCR was used to detect the expression of miR-455 and the mRNA levels of glucose-regulated protein 78 （ Grp78） and caspase-12 in the myo-cardium.RESULTS：Compared with control group, EC apoptosis in IR group was significantly increased （P〈0.05）. Compared with IR group , EC apoptosis in IR ＋Cordy group decreased significantly （ P〈0.05 ） .Compared with control group, swelling of mitochondria , irregular membrane , loose wrinkles with vacuoles , disappeared matrix granules , irregular nuclear membrane , chromatin condensation , disappeared nucleoli and even small apoptosis body in the EC were found in IR group.Compared with IR group , the symptoms in IR ＋Cordy group were greatly improved .Compared with control group, the mRNA expression of Grp78 and caspase-12 as well as the miR-455 level in IR group was increased （P〈0.05）. Compared with IR group , the mRNA expression of Grp78 and caspase-12, as well as the miR-455 level in IR＋Cordy group was decreased （P〈0.05）.CONCLUSION：Cordycepin attenuates myocardial EC apoptosis , down-regulates the expres-sion of miR-455, a

关 键 词：虫草素 缺血再灌注损伤 内质网应激 微小RNA-455 细胞凋亡 

分 类 号：R363[医药卫生—病理学]