尼可地尔对糖尿病心肌病大鼠心肌细胞凋亡的干预作用

Effect of nicorandil on cardiomyocyte apoptosis in diabetic cardiomyopathy rats

目的探讨尼可地尔对糖尿病心肌病(diabetic cardiomyopathy, DCM)大鼠心肌细胞凋亡的干预作用。方法取雄性SD大鼠32只,随机分为对照组(A组)、DCM组(B组)、尼可地尔干预组(C组)、格列本脲干预组(D组),每组各8只。A组予常规饲料喂养,未干预;B、C、D组予高脂高热量饮食喂养6周诱导胰岛素抵抗,小剂量链脲佐菌素腹腔注射建立DCM模型,继续高脂高糖饲料喂养2周后开始干预,B组予0.9%氯化钠溶液灌胃(4 mg·kg^(-1)·d^(-1)),C组予尼可地尔灌胃(10 mg·kg^(-1)·d^(-1)),D组予格列本脲灌胃(5mg·kg^(-1)·d^(-1)),连续干预28 d。麻醉动物,心脏采血,处死后留取心脏标本。检测血糖及CRP水平;western blot法检测心肌组织caspase-3、cleaved caspase-3表达水平;ELISA法检测血浆TNF-α表达水平。结果与A组比较,B、C、D组血糖均明显升高(P <0.05),且B、C、D组间血糖及CRP水平的差异均无统计学意义(P> 0.05)。与A组比较,B组、D组大鼠caspase-3、cleaved caspase-3及TNF-α表达表达水平均明显升高(均P <0.05);与B组比较,C组大鼠caspase-3、cleaved caspase-3及TNF-α表达水平明显降低(均P <0.05);与C组比较,D组大鼠caspase-3、cleaved caspase-3及TNF-α表达水平均明显升高(均P <0.05)。结论尼可地尔可通过减轻细胞凋亡发挥其心肌保护作用,且对血糖代谢无影响。

Objective To research the effect of nicorandil on cardiomyocyte apoptosis in diabetic cardiomyopathy(DCM) rats. Methods Thirty-two male Sprague-Dawley rats were randomly divided into control group A and DCM group B, nicorandil group C and glibenclamide group D. Group A was fed with conventional feed without intervention. Other groups were given measures inducing Insulin resistance by high-fat and high-calorie diet for 6 weeks, and the DCM model was established by intraperitoneal injection of streptozocin STZ(low dose streptozocin).After 2 weeks of continuous feeding with high fat and high sugar diet, the group B was given normal saline(4 mg/kg), group C was given nicorandil(10 mg/kg), meanwhile, group D was given glibenclamide(5 mg/kg) for 28 days. Then we anesthetized animals, collected the heart blood, after the specimens of the heart were taken after. Blood glucose and CRP were measured in each group, the expression of caspase-3, cleaved caspase-3 were detected by western blot method, TNF-α in plasma by Elisa. Results compared with group A, the blood glucose level in group B, C and D was significantly higher than that in group A(P<0.05), and there was no difference among group B, C and D(P>0.05), there was no significant difference in CRP among B, C and D group(P>0.05). Compared with group A, the expression of caspase-3、cleaved caspase-3 and TNF-α in group C and D were significantly higher than that in group A(P<0.05), there was no significantly difference in the expression between group C and A(P>0.05). Compared with group B, the expression in group C was significantly lower than that in group B(P<0.05). the expression in group D was not significantly higher than that in group B(P>0.05). Conclusion nicorandil can protect myocardium from apoptosis and has no effect on blood glucose metabolism.