戊酸雌二醇与氯吡格雷联用对去卵巢大鼠心肌缺血再灌注损伤的影响  

Effects of estradiol valerate combined with clopidogrel on myocardial ischemia-reperfusion injury in ovariectomized rats

作　　者：丁国民[1] 尚云鹏[2] 卢小丽[1] DING Guo-Min;SHANG Yun-Peng;LU Xiao-Li(Anji People’s Hospital,Huzhou,Zhejiang 313300,China)

机构地区：[1]安吉县人民医院,浙江湖州313300 [2]浙江大学附属第一医院,浙江杭州310006

出　　处：《中国妇幼保健》2021年第24期5768-5773,共6页Maternal and Child Health Care of China

基　　金：浙江省医学会临床科研基金项目(2019ZYC-A131)。

摘　　要：目的探讨戊酸雌二醇与氯吡格雷联用对去卵巢大鼠心肌缺血再灌注损伤的影响,为临床用药提供理论依据。方法选取雌性SD大鼠100只,分为2批,每批50只,随机分为5组,每组10只,分别为假手术组、模型组、戊酸雌二醇组(0.1 mg/kg)、氯吡格雷组(7 mg/kg)及戊酸雌二醇(0.1 mg/kg)与氯吡格雷(7 mg/kg)联用组。除假手术组外,其余各组均彻底摘除卵巢建立围绝经期模型,摘除卵巢后开始给药,给药7 d后开始手术,并结扎冠状动脉左前降支30 min,复灌120 min建立心肌缺血再灌注模型。第1批用四氮唑红(TTC)染色法检测去卵巢大鼠心肌缺血再灌注损伤后心脏梗死面积,试剂盒检测血浆SOD活力、MDA含量、LDH活力及CK活力指标的影响;第2批使用苏木精-伊红(HE)染色法检测去卵巢大鼠心肌缺血再灌注损伤后心脏组织病理学改变,Western blot法检测心肌组织中SIRT1、ac-p53、Bax、Bcl-2及c-caspase3蛋白表达情况。结果与假手术组相比,模型组大鼠心脏梗死面积、组织病理学评分、MDA含量、LDH活力、CK活力、ac-p53、Bax蛋白表达量及c-caspase3蛋白表达量均显著高于假手术组(均P<0.05),SOD活力、SIRT1蛋白表达量及Bcl-2蛋白表达量显著低于假手术组,差异均有统计学意义(均P<0.05)。与模型组相比,联合用药组大鼠心脏梗死面积、组织病理学评分、血浆CK活力、MDA含量、血浆LDH活力、ac-p53蛋白表达量、Bax蛋白表达量及c-caspase3蛋白表达量显著下降,差异均有统计学意义(均P<0.05),血浆SOD活力、SIRT1蛋白表达量、Bcl-2蛋白表达量显著上升,差异均有统计学意义(均P<0.05)。联合用药组药效在各指标上不同程度优于2个单独给药组。氯吡格雷与戊酸雌二醇具有交互作用(P<0.05)。结论戊酸雌二醇与氯吡格雷两者联合用药药效优于戊酸雌二醇和氯吡格雷单独用药药效,可能是通过上调SIRT1通路抗凋亡实现的。Objective To investigate the effects of estradiol valerate combined with clopidogrel on myocardial ischemia-reperfusion injury in ovariectomized rats,and to provide theoretical basis for clinical medication.Methods A total of 100 female SD rats were randomly divided into 5 groups with 10 rats in each group,including sham operation group,model group,estradiol valerate(0.1 mg/kg),clopidogrel group(7 mg/kg)and estradiol valerate(0.1 mg/kg)combined with clopidogrel(7 mg/kg).Except for the sham operation group,all ovaries were completely removed to establish perimenopausal model.After ovaries were removed,the operation was started 7 days later,and the left anterior descending coronary artery was ligation for 30 min.The myocardial ischemia reperfusion model was established after 120 minutes.In the first group,the area of heart infarction after myocardial ischemia-reperfusion injury in ovariectomized rats was detected by TTC staining,and the effects of SOD activity,MDA content,LDH activity and CK activity indexes in plasma were detected by dose box.In the second group,hematoxylin-eosin(HE)staining was used to detect the histopathological changes of the ovariectomized myocardium after ischemia-reperfusion injury,and the protein levels of SIRT1,ac-p53,Bax,Bcl-2 and c-caspase3 in the myocardium were detected by Western blot.Results Compared with sham operation group,the infarct size,histopathological score,MDA content,LDH activity,CK activity,ac-p53,Bax protein expression and c-caspase3 protein expression in model group were significantly higher than those in sham operation group,the differences were statistically significant(all P<0.05).SOD activity,SIRT1 protein expression and Bcl-2 protein expression were significantly lower than those in sham operation group,the differences were statistically significant(all P<0.05).Compared with model group,histopathological score of heart infarction surface,plasma CK activity,MDA content,plasma LDH activity,ac-p53 protein expression level and Bax protein surface of rats in combined t

关 键 词：戊酸雌二醇 围绝经期 心肌缺血再灌注 氯吡格雷 联合用药 

分 类 号：R332[医药卫生—人体生理学]