复方麝香注射液通过抑制内质网应激对大鼠心肌缺血/再灌注损伤起保护作用  

Protective effect of Compound Musk Injection on myocardial ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress

作　　者：杨柳[1] 苑亚静[2] 刘雪[1] Yang Liu;Yuan Yajing;Liu Xue(The First Affiliated Hospital of Dalian Medical University,Dalian 116021,Liaoning,China;Tianjin Medical Unirersiry Cancer Institute and Hospital,Tianjin 300060,China)

机构地区：[1]大连医科大学附属第一医院,辽宁大连116021 [2]天津医科大学肿瘤医院,天津300060

出　　处：《中国中西医结合急救杂志》2020年第5期616-619,共4页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：国家自然科学基金(8150114)。

摘　　要：目的 观察复方麝香注射液对大鼠心肌缺血/再灌注(I/R)损伤的作用,并探讨其作用机制.方法 将36只成年雄性SD大鼠按随机数字表法分为假手术组、I/R模型组、药物干预组,每组12只.采用结扎大鼠左冠状动脉(冠脉)前降支30min后,再灌注120min的方法,复制I/R损伤模型;假手术组仅在冠脉前降支下穿线而不结扎.药物干预组于术前7d连续腹腔注射复方麝香注射液2mL/kg;假手术组和I/R模型组术前给予等量生理盐水.观察不同处理方法各组心肌梗死面积和心肌细胞凋亡指数(AI)的变化;采用反转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹试验(WesternBlot)检测葡萄糖调节蛋白78(GRP78)、CAAT区/增强子结合蛋白同源蛋白(CHOP)和天冬氨酸特异性半胱氨酸蛋白酶12(caspase-12)的mRNA和蛋白表达水平.结果 I/R模型组心肌梗死面积〔(40.81±5.74)%比(9.27±2.09)%〕、AI〔(35.26±3.49)%比(2.52±0.41)%〕均较假手术组明显升高(均P<0.05);药物干预组大鼠心肌梗死面积〔(32.63±3.78)%比(40.81±5.74)%〕和AI〔(19.73±2.04)%比(35.26±3.49)%〕均明显低于I/R模型组(均P<0.05);I/R模型组GRP78、CHOP、caspase-12mRNA(2-ΔΔCt)和蛋白(灰度值)表达水平均明显高于假手术组(GRP78mRNA:3.79±0.23比1.00±0.00,CHOPmRNA:3.05±0.10比1.00±0.00,caspase-12mRNA:4.59±0.13比1.00±0.00;GRP78蛋白:3.31±0.14比1.00±0.00,CHOP蛋白:2.16±0.14比1.00±0.00,caspase-12蛋白:4.27±0.15比1.00±0.00,均P<0.05);药物干预组GRP78、CHOP、caspase-12mRNA(2-ΔΔCt)和蛋白(灰度值)表达水平均明显低于I/R模型组(GRP78mRNA:1.96±0.10比3.79±0.23,CHOPmRNA:2.26±0.07比3.05±0.10,caspase-12mRNA:2.84±0.29比4.59±0.13;GRP78蛋白:2.39±0.06比3.31±0.14,CHOP蛋白:1.51±0.11比2.16±0.14,caspase-12蛋白:3.01±0.14比4.27±0.15,均P<0.05).结论 复方麝香注射液通过抑制内质网应激对大鼠心肌I/R损伤起到保护作用.Objective To ohserve the protective effect of Compound Musk Injection on myocardial ischemia/reperfusion(I/R)injury in rats and its mechanism investigation.Methods According to random number table method,36 adult male Sprague-Dawley(SD)rals were divided into three groups:sham operation,I/R model and drug itevention groups,with 12 rats in each group.The rat I/R injury model was replicated by ligation of the anterior descending branch of lefi coronary artery for 30 minutes and then reperfusion for 120 minutes;in the sham operation group,only was under the anterior descending coronary artery threaded without ligation.In drug intervention group,2mL/kg Compound Musk injection preparation was injected into the abdominal cavity every day for consecutive 7 days before operation.The sham operation and I/R model groups were given the equal amount of normal saline before operation.The changes of miocardial infarction area and cardiomyocyte apoptosis index(AI)in different groups were observed;the mRNA and protein levels of glucose regulated protein 78(CRP78),CAAT region/enhancer binding protein homologous protein(CHOP)and aspartie acid specifie cysteine protease 12(caspase-12)were dected by reverse transcription polymerase chain reaction(RT-PCR)and Western Blot,respetively.Results The myocardial infarction area[(40.81±5.74)% vs.(9.27±2.09)%]and AI [(35.26±3.49)% vs.(2.52±0.41)%]in IR model group were significantly higher than those in sham operation group(both P<0.05).The myocardial infaretion area[(32.63±3.78)%vs.(40.81±5.74)%]and AI[(19.73±2.04)%vs.(35.26±3.49)%]in drug intervention group were significantly lower than those in I/R model goup(both P<0.05).The expression levels of GRP78,CHOP,caspase-12 mRNA(2^-ΔΔCt)and protein(gray value)in I/R model group were significantly higher than those in sham operation group(GRP78 mRNA:3.79±0.23 vs.1.00±0.00,CHOP mRNA:3.05±0.10 vs.1.00±0.00.caspase-12 mRNA:4.59±0.13 vs.1.00±0.00;GRP78 protein:3.31±0.14 v8.1.00±0.00,CHOP protein:2.16±0.14 vs.1.00±0.00,caspase-12 pr

关 键 词：缺血/再灌注损伤 心肌 内质网应激 复方麝香注射液 

分 类 号：R73[医药卫生—肿瘤]