机构地区:[1]广西中医药大学,南宁530001 [2]广西中医药大学第一附属医院,南宁530023 [3]广西中医学校 [4]广西国际壮医医院
出 处:《中西医结合心脑血管病杂志》2023年第22期4101-4106,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基 金:国家自然科学基金课题(No.81673891);国家中医临床研究基地业务建设第二批科研专项课题(No.JDZX2015146);广西自然科学基金项目(No.2017GXNSFAA198302);广西名老中医工作室建设项目,编号:桂中医药办发[2019]36号。
摘 要:目的:观察强心汤对大鼠心肌组织半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、Bcl-2家族相关x蛋白(Bax)、B细胞淋巴瘤/白血病-2(Bcl-2)表达的影响,探讨强心汤调控心肌细胞凋亡的可能作用机制。方法:采用结扎大鼠冠状动脉左前降支的方式建立慢性心力衰竭(CHF)大鼠模型,将50只SD大鼠按随机数字表法分为5组,分别为模型组、金属蛋白酶相关蛋白1(OMA1)封闭组、强心汤组、OMA1封闭+强心汤组、假手术组,其中假手术组大鼠的左冠状动脉只穿线不结扎。经心脏彩超检测提示大鼠左室射血分数(LVEF)下降20%~30%左右判定造模成功,成功造模后第2天开始,相应实验组分别进行OMA1基因封闭,等剂量强心汤混悬液、生理盐水灌胃处理,4周后使用心脏彩超检测各组大鼠心脏左室心功能指标,即左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、LVEF。采用逆转录聚合酶链式反应(qRT-PCR)、蛋白质免疫印迹法(Western Blot)检测大鼠心肌组织中OMA1及Caspase-3、Bcl-2、Bax的mRNA和蛋白表达情况。结果:与假手术组相比,模型组大鼠LVEDD、LVESD升高,LVEF降低,心肌组织OMA1及Caspase-3、Bax mRNA和蛋白表达均升高,Bcl-2 mRNA和蛋白表达均下降(P<0.05)。各干预组与模型组比较,干预组大鼠左室心功能明显改善,心肌组织的OMA1及Caspase-3、Bax、Bcl-2 mRNA和蛋白表达均优于模型组;各干预组间比较上述指标改善情况显示OMA1封闭组优于强心汤组,OMA1封闭+强心汤组优于OMA1封闭组和强心汤组(P<0.05)。结论:强心汤可能通过上调Bcl-2和下调OMA1、Bax、Caspase-3的表达水平,调控心肌线粒体功能和心肌凋亡,从而保护心肌,改善心功能。Objective:To the possible mechanism of Qiangxin Decoction on regulating myocardial apoptosis.Methods:The chronic heart failure(CHF)rat model was established by ligation of the left anterior descending coronary artery in rats,and 50 SD rats were randomly divided into model group,metalloproteinase-related protein 1(OMA1)block group,Qiangxin Decoction group,OMA1 block+Qiangxin Decoction group,and sham operation group.At the second day after successful modeling,the corresponding experimental groups were treated with OMA1 gene sealing,equal dose of Qiangxin Decoction suspension and normal saline intragastrial treatment respectively.After 4 weeks,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)were detected by cardiac color Doppler echocardiography.The mRNA and protein expressions of OMA1,Caspase-3,Bcl-2,and Bax in rat myocardium were detected by reverse transcription polymerase chain reaction(qRT-PCR)and Western Blot.Results:Compared with sham operation group,LVEDD and LVESD values in model group increased,LVEF decreased,mRNA and protein expressions of OMA1,Caspase-3,and Bax were increased,and mRNA and protein expressions of Bcl-2 decreased(P<0.05).Compared with model group,the left ventricular function of the intervention group significantly improved,and the expressions of OMA1,Caspase-3,Bax mRNA,Bcl-2 mRNA and protein in the myocardial tissue of the intervention group were also better than that of model group.The above indicators in OMA1 block group was superior to Qiangxin Decoction group,and OMA1 block+Qiangxin Decoction group was superior to OMA1 block group and Qiangxin Decoction group(P<0.05).Conclusion:Qiangxin Decoction may protect myocardium and improve cardiac function by up-regulating the expression levels of Bcl-2 and down-regulating OMA1,Bax,and Caspase-3,regulating the mitochondrial function and myocardial apoptosis.
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