摘要
目的:探究暖心康通过调节线粒体相关内质网膜(MAMs)抑制心肌细胞凋亡对缺血再灌注致心肌损伤小鼠的保护机制。方法:将21只SPF级雄性C57BL/6J小鼠随机分为假手术组、模型组和暖心康组,每组7只。模型组和暖心康组建立小鼠心肌缺血再灌注损伤模型。术后暖心康组灌胃给予暖心康溶液1.65 g·kg-1·d-1,其余两组灌胃给予等量0.9%氯化钠溶液,连续4周。超声心动检测小鼠心功能情况,天狼猩红染色、HE染色分别检测小鼠心脏胶原纤维沉积和心肌细胞形态变化,Western blot检测小鼠心脏Mfn2蛋白表达水平,荧光染色检测小鼠原代心肌细胞MAMs共定位情况,TUNEL染色检测小鼠心肌细胞凋亡情况。结果:与假手术组比较,模型组小鼠心功能明显下降,心脏胶原纤维面积明显增多,心肌细胞肥大、排列紊乱,炎性细胞增多,心脏中Mfn2蛋白表达水平显著升高(P<0.01),MAMs耦联部分显著增多(P<0.01),心肌细胞凋亡数量亦显著增多(P<0.01);与模型组比较,暖心康组小鼠心功能在2、4周得到显著改善(P<0.01),心脏纤维化程度和病理形态改变减轻,心脏中Mfn2蛋白表达水平显著降低(P<0.01),MAMs耦联部分和心肌细胞凋亡数量均显著减少(P<0.01)。结论:暖心康可改善心肌缺血再灌注心脏心室重构,其作用机制可能是通过下调Mfn2蛋白表达,从而减少MAMs耦联,抑制心肌细胞凋亡实现的。
Objective:To explore the protective mechanism of Nuanxinkang(NXK) over regulating mitochondrial-related endoplasmic reticulum membrane(MAMs) to inhibit cardiomyocyte apoptosis in mice with myocardial injury caused by ischemiareperfusion.Methods:A total of 21 SPF C57BL/6J male mice were randomly divided into sham operation(SHAM) group,model group(I/R) and Nuanxinkang group(NXK+I/R),7 mice in each group.Echocardiography was used to detect the cardiac function of the mice in each group.Sirius red staining and HE staining were used to detect the collagen fiber deposition and cardiomyocytes pathological changes in mice.Western blot was used to detect the expression level of Mfn2 protein,and fluorescence staining was used to detect the co-localization of MAMs.Tunel staining was used to detect the apoptosis of cardiomyocytes in each group of mice.Results:Compared with the SHAM group,the cardiac function in the I/R group was significantly decreased,the collagen fiber area of heart increased significantly,and the cardiomyocytes were hypertrophy and disordered,inflammatory cells increased.In addition,the expression level of Mfn2 protein in the heart was obviously increased(P<0.01),and the co-localization of MAMs and the number of cardiomyocyte apoptosis increased significantly(P<0.01).Compared with the I/R group,the cardiac function of the mice in the NXK+I/R group was significantly improved in 2 and 4 weeks(P<0.01).Besides,the degree of cardiac fibrosis and pathological changes were reduced,the level of Mfn2 protein was significantly decreased(P<0.01),and the coupling part of MAMs and the apoptotic number of cardiomyocytes were also significantly decreased(P<0.01).Conclusion:NXK improves myocardial ischemia-reperfusion cardiac ventricular remodeling,and its mechanism may be achieved by reducing the coupling of MAMs and inhibiting cardiomyocytes apoptosis.
作者
江佳林
陈梓欣
董鑫
林祉均
关卓骥
黎欢
王陵军
冼绍祥
JIANG Jia-lin;CHEN Zi-xin;DONG Xin;LIN Zhi-jun;GUAN Zhuo-ji;LI Huan;WANG Ling-jun;XIAN Shao-xiang(First Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Lingnan Medical Research Center of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第8期4647-4651,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(No.81973777)
国家自然科学基金青年科学基金项目(No.82004293)。
关键词
暖心康
心肌缺血再灌注损伤
线粒体相关内质网膜
细胞凋亡
Nuanxinkang
Myocardial ischemia reperfusion injury
Mitochondrial-associated endoplasmic reticulum
Apoptosis
