摘要
目的:基于内质网应激(ERS)探究暖心康治疗小鼠心肌缺血/再灌注(I/R)损伤所致慢性心力衰竭(CHF)的作用和机制。方法:24只SPF级C57BL/6J雄性小鼠随机分为假手术组、模型组、暖心康组,采用结扎小鼠冠状动脉左前降支建立I/R心力衰竭模型,术后1天起,暖心康组给予暖心康灌胃(1.65 g·kg^(-1)·d^(-1)),假手术组及模型组给予等量0.9%氯化钠溶液灌胃,每日1次,持续6周;采用超声心动图检测小鼠心功能、天狼猩红染色观察小鼠心肌纤维化、TUNEL染色检测心肌细胞凋亡、qPCR检测心肌ERS相关基因mRNA表达水平。结果:与假手术组比较,模型组左室射血分数(EF)、缩短分数(FS)显著降低(P<0.01),表明I/R心力衰竭模型构建成功,与模型组比较,暖心康组EF、FS得到显著改善(P<0.01);天狼猩红染色提示暖心康能改善I/R小鼠心肌纤维化;TUNEL染色显示暖心康能减少I/R小鼠心肌细胞凋亡;检测心肌ERS相关基因mRNA表达水平,与假手术组比较,模型组葡萄糖调节蛋白78(Grp78)、CCAAT增强子结合蛋白同源蛋白(Chop)、c-Jun氨基末端激酶1(Jnk1)、半胱天冬酶12(Caspase 12)、Bcl-2相关X蛋白(Bax)mRNA表达水平升高,B淋巴细胞瘤2(Bcl-2)m RNA表达水平降低(P<0.05,P<0.01),而与模型组比较,暖心康组Grp78、Chop、Jnk1、Caspase 12、Bax mRNA表达水平下降,Bcl-2 mRNA表达水平升高(P<0.05,P<0.01)。结论:暖心康可能通过下调心肌细胞ERS,减少心肌细胞凋亡,从而减轻I/R心力衰竭小鼠的心肌纤维化,改善心功能。
Objective:To explore the effect and mechanism of Nuanxinkang(NXK)in the treatment of chronic heart failure(CHF)caused by myocardial ischemia-reperfusion(I/R)injury in mice based on endoplasmic reticulum stress(ERS).Methods:A total of 24 SPF C57BL/6J male mice were randomly divided into Sham operation group(Sham),model group(I/R),and Nuanxinkang group(I/R+NXK).The I/R model was established by ligating the left anterior descending coronary artery in mice.From 1 day after the operation,the I/R+NXK group was given NXK intragastric administration(1.65 g·kg^(-1)·d^(-1)),while the Sham group and I/R group were given the same amount of normal saline gavage,once a day for 6 weeks.After 6 weeks,the cardiac function of the mice was detected by echocardiography.Sirius red staining was used to observe the myocardial fibrosis,and TUNEL staining was used to detect cardiomyocyte apoptosis.qPCR was used to detect the mRNA expression of myocardial endoplasmic reticulum stress-related genes.Results:Compared with the Sham group,the left ventricular ejection fraction(EF)and fractional shortening(FS)of the I/R group were significantly decreased(P<0.01),indicating that the I/R heart failure model was successfully constructed.Compared with the I/R group,EF and FS of the I/R+NXK group were significantly improved(P<0.01).Sirius red staining indicated that NXK could improve myocardial fibrosis in I/R heart failure mice.TUNEL staining showed that NXK could reduce cardiomyocyte apoptosis in I/R injury mice.The mRNA expression levels of endoplasmic reticulum stress-related genes were detected,compared with the Sham group,the mRNA expression of glucose-regulated protein 78(Grp78),CCAAT enhancer binding protein homologous protein(Chop),c-Jun N-terminal kinase 1(Jnk1),cysteinyl aspartate specific protease 12(Caspase 12),and Bcl-2-associated X protein(Bax)in I/R group increased,the expression of B-cell lymphoma-2(Bcl-2)decreased(P<0.05,P<0.01),while compared with the I/R group,the mRNA expression of Grp78,Chop,Jnk1,Caspase 12,and Bax in I/R+NXK group decreased,the expression of Bcl-2 increased(P<0.05,P<0.01).Conclusion:NXK may reduce cardiomyocyte apoptosis by downregulating myocardial ERS,thereby reducing myocardial fibrosis and improving cardiac function in I/R heart failure mice.
作者
关卓骥
陈梓欣
江佳林
董鑫
林祉均
李玄
王陵军
方红城
冼绍祥
GUAN Zhuo-ji;CHEN Zi-xin;JIANG Jia-lin;DONG Xin;LIN Zhi-jun;LI Xuan;WANG Ling-jun;FANG Hong-cheng;XIAN Shao-xiang(Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Guangzhou Key Laboratory for Traditional Chinese Medicine Prevention and Treatment of Chronic Heart Failure,Guangzhou 510405,China;Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine,Shenzhen 518033,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第11期6791-6795,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81973777,No.82004293)
广东省基础与应用基础研究基金项目(No.2019A1515110374)
广东省教育厅项目(No.2019KQNCX020)
深圳市“医疗卫生三名工程项目”(No.SZZYSM202106006)。
关键词
慢性心力衰竭
益气活血法
内质网应激
心肌纤维化
暖心康
机制
心肌缺血/再灌注损伤
动物模型
Chronic heart failure(CHF)
Method of benefiting qi and activating blood
Endoplasmic reticulum stress(ERS)
Myocardial fibrosis
Nuanxinkang
Mechanism
Myocardia ischemia-reperfusion injury
Animal model
