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目的:检测ATP敏感的钾通道激活剂尼可地尔对实验性糖尿病大鼠的心肌纤维化的影响。方法:链脲佐菌素诱导的糖尿病SD大鼠,随机分为3组,一组作为对照,一组口服安慰剂,一组给予(10mg/kg)尼可地尔12周。实验结束后分别测量心功能等指标,并检测心肌组织血栓素蛋白(TSP)-1、胶原、血管紧张素Ⅱ(AngⅡ)、TGF-β1、磷酸化p38MAPK等指标的水平。结果:与对照组比较,糖尿病大鼠12周时左心室功能受损。糖尿病大鼠心肌组织AngⅡ、TSP-1高表达,心肌组织p38MAPK水平增高,心肌间质纤维化明显。尼可地尔处理过的糖尿病大鼠,左室功能以及心肌间质纤维化程度显著减轻,其心肌组织TSP-1mRNA和蛋白质表达与p38MAPK途径均下调。结论:TSP-1在糖尿病心肌纤维化发生机制中起重要作用,与p38MAPK途径激活以及后续TGFβ-1以及胶原过度表达密切相关。尼可地尔对糖尿病心肌纤维化有较好逆转作用,其机制与抑制p38途径以及纤维化过程有关。
Objective: To investigate the effect of nicorandil, an ATP-sensitive potassium channel activator, on myocardial fibrosis in experimental diabetic rats. Methods: Streptozotocin-induced diabetic SD rats were randomly divided into three groups. One group served as a control group. One group received oral placebo and the other group (10 mg / kg) nicorandil for 12 weeks. At the end of the experiment, the cardiac function and other indexes were measured. The level of TSP-1, collagen, angiotensin Ⅱ, TGF-β1 and phosphorylated p38MAPK were detected. Results: Compared with the control group, left ventricular function was impaired at 12 weeks in diabetic rats. The expression of AngⅡ and TSP-1 in myocardium of diabetic rats was increased, the level of p38MAPK in myocardium was increased, and the myocardial interstitial fibrosis was obvious. Nicorandil treatment of diabetic rats, left ventricular function and myocardial interstitial fibrosis significantly reduced the myocardial TSP-1mRNA and protein expression and p38MAPK pathway were down. CONCLUSION: TSP-1 plays an important role in the pathogenesis of diabetic myocardial fibrosis and is closely related to the activation of p38 MAPK pathway and the subsequent TGFβ-1 and collagen overexpression. Nicorandil has a good reversal of diabetic myocardial fibrosis, the mechanism of inhibition of p38 pathway and the process of fibrosis.