摘要
目的:观察真武汤通过Sirt1信号转导通路蛋白抑制心肌细胞凋亡的影响,探讨真武汤治疗心力衰竭的机制。方法:复制心梗后心衰模型,通过检测脑钠肽(BNP)来确定心衰造模成功,将心力衰竭大鼠随机分为治疗组(真武汤低、中、高剂量组)、阳性药物对照组(卡托普利)、模型组,分别给药15 d,同时设空白对照组。通过彩超测量左室射血分数(LVEF)、左室短轴缩短率(LVFS)等评价心功能,用酶联免疫法(ELISA)检测心衰大鼠血清中BNP,电镜观察心肌细胞内线粒体形态和数量变化,Westernblotting来检测心肌Bax,Bcl-2,Caspase-3,和Sirt-1的表达。结果:1.与正常组相比,治疗组与模型组的BNP表达均升高;2.与正常组相比,模型组LVEF、LVFS水平明显降低(P〈0.01);与模型组相比,中、高剂量组LVEF、LVFS水平明显升高(P〈0.01)。3.电子显微镜可观察到模型组大鼠的心肌细胞线粒体数量下降以及移位,并出现其他形态学改变,主要表现为线粒体数量和大小的变化,治疗后,数量和大小均有提升。4.与正常组比较,各组sirt-1蛋白表达均有不同程度减少,Bax及Caspase-3蛋白表达显著增加,Bcl-2的表达有不同程度的降低;与模型组相比,各治疗组sirt-1的表达均有所升高,其中阳性药物及真武汤中高剂量组的表达较高,各组Bax、Caspase-3的表达均有所下降,阳性药物对照组及真武汤中高剂量组表达最低,各治疗组Bcl-2的表达均升高,阳性药物对照组及中药中高剂量组较显著。结论:真武汤可通过调节心肌细胞中线粒体通路,影响凋亡相关蛋白的表达,抑制心肌细胞的凋亡,从而延缓充血性心衰的发展。SIRT1信号通路在抑制心力衰竭心肌细胞的凋亡中起着关键的作用。
Objective: To observe the effect of Zhenyu Decoction on cardiomyocyte apoptosis induced by SIRT1 signal transduction pathway protein and explore the mechanism of Zhenwu Decoction in treating heart failure. Methods: Heart failure model was established by the method of heart failure. Heart failure rats were randomly divided into treatment groups(Zhenwu Decoction medium and high dose groups),positive drug control group(captopril),model group. These groups were respectively given medication for 15 days and the blank control group was set up at the same time. The left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) were used to evaluate cardiac function. The serum BNP was measured by enzyme-linked immunosorbent assay(ELISA). The mitochondrial morphology of cardiomyocytes was observed by electron microscopy and the number of changes was also observed. Western blotting was used to detect the expressions of Bax,Bcl-2,Caspase-3,and Sirt-1 in myocardium. Results:Compared with the normal group,the expressions of BNP in the treatment group and the model group were higher than those in the normal group. Compared with the normal group,the levels of LVEF and LVFS in the model group were significantly lower than that in the normal group(P〈0. 01). The levels of LVEF and LVFS in middle and high dose groups were significantly increased(P〈0. 01). Electron microscopy showed that the number of mitochondria in the model group decreased and the number of mitochondria was decreased and the morphological changes were observed. The main changes were the number and size of mitochondria. After treatment,the number and size of mitochondria were improved. Compared with the normal group,the expression of Sirt-1 protein was decreased in different groups. The expressions of Bax and Caspase-3 protein were significantly increased and the expression of Bcl-2 was decreased in different groups. Compared with the model group,the expressions of Bax and Caspase-3 in the high dose group were significantly higher than that in the control group and the high dose group. The expression of Bcl-2 in the treatment group was higher than that in the control group and the high dose group. Conclusion: Zhenwu Decoction can delay the development of congestive heart failure by regulating mitochondrial pathway in myocardial cells,affecting the expression of apoptosis-related proteins and inhibiting the apoptosis of cardiomyocytes. SIRT1 signaling pathway plays a key role in the inhibition of cardiomyocyte apoptosis in heart failure.
作者
李峥
李文杰
尚雪莹
于凯洋
LI Zheng1, LI Wenjie2 , SHANG Xueying1, YU Kaiyang1(1. Liaoning University of TCM, Shenyang 110847, Liaoning, China ; 2. The Affiliated Hospital of Liaoning University of TCM, Shenyang 110032, Lia0ning, Chin)
出处
《中华中医药学刊》
CAS
北大核心
2018年第5期1062-1067,共6页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81173184)