Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, China.
Am J Chin Med. 2009;37(6):1059-68. doi: 10.1142/S0192415X09007491.
The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dP/dt(max) and t-dP/d(max)t, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and +/- dP/dt(max), increased LVEDP, and prolonged t-dP/dt(max) than normal rats; (2) LVSP and +/- dP/dt(max) in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t-dP/dt(max) were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.
本研究旨在探讨心脏功能变化与两种主要心肌骨架蛋白肌联蛋白和nebulin 的基因表达之间的关系,以及绞股蓝皂苷对糖尿病心肌病大鼠这些基因表达的影响。将 40 只 Sprague-Dawley 大鼠随机分为三组:对照组、糖尿病心肌病组和绞股蓝皂苷治疗的糖尿病心肌病组。大鼠腹腔内注射链脲佐菌素(STZ,55mg/kg)诱导糖尿病心肌病。大鼠患糖尿病 7 周后,绞股蓝皂苷治疗组大鼠每天口服绞股蓝皂苷 100mg/kg 治疗 6 周。同时,糖尿病心肌病组和对照组给予纯净水。随后,测定心脏功能,包括左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、+/-dp/dt(max)和 t-dp/dt(max),以及心肌中肌联蛋白和 nebulin 的 mRNA 含量和蛋白。结果表明:(1)糖尿病心肌病大鼠的 LVSP 和 +/-dp/dt(max)降低,LVEDP 升高,t-dp/dt(max)延长;(2)绞股蓝皂苷治疗的糖尿病心肌病大鼠的 LVSP 和 +/-dp/dt(max)明显高于未给予绞股蓝皂苷的大鼠,LVEDP 和 t-dp/dt(max)明显低于未给予绞股蓝皂苷的大鼠;(3)糖尿病心肌病大鼠的肌联蛋白和 nebulin 的 mRNA 含量和蛋白明显低于对照组大鼠,绞股蓝皂苷对糖尿病心肌病大鼠肌联蛋白和 nebulin 的 mRNA 和蛋白表达水平无影响。结论:(1)糖尿病心肌病大鼠的心脏功能以及肌联蛋白和 nebulin 的 mRNA 表达降低;(2)绞股蓝皂苷可保护心脏肌肉及其功能免受糖尿病损害,绞股蓝皂苷的这些有益作用不是通过改变肌联蛋白和 nebulin 的表达来实现的。