他汀改善实验性糖尿病内皮细胞功能的研究

Statin improved endothelial dysfunction in experimental diabetes mellitus

目的研究阿托伐他汀对链脲佐菌素(STZ)诱导的Ⅰ型糖尿病大鼠血管内皮功能不良的影响。方法8周龄SD雄性大鼠两次腹腔注射STZ诱发实验性I型糖尿病,以不足产生降血脂作用小剂量阿托伐他汀对糖尿病大鼠进行干预,应用在体后肢自动灌注模式(autoperfused hindlimb model)测定大鼠体内血管内皮依赖性舒张功能,并观察主动脉壁组织中内皮一氧化氮合成酶(eNOS)mRNA的表达。结果与大鼠正常对照组相比,糖尿病组大鼠内皮依赖性血管舒张功能显著下降(P<0.05),血清NO含量明显降低(P<0.05),主动脉壁组织中eNOS mRNA表达下调(P<0.05)。与糖尿病对照组相比,阿托伐他汀干预组大鼠内皮依赖性血管舒张显著增加(P<0.05),血清NO含量显著升高(P<0.05),主动脉壁组织中一氧化氮合成酶(eNOS)mRNA的表达显著上调(P<0.05)。结论低剂量阿托伐他汀能显著改善链脲佐菌素诱导的Ⅰ型糖尿病大鼠血管内皮依赖性舒张功能,其机制与阿托伐他汀降血脂作用无关。

Objective To investigate the effects of atorvastatin on the endothelial dysfunction in streptozotocin（SIZ）-induced type Ⅰ diabetic rats. Methods Diabetes melhtus was induced in 8 weeks old male Sprague Dawley （SD） rats by two times intraperitoneal injection of STZ. Low dose of atorvastatin, which had no effects on the serum lipid profile, were administered in diabetic rats. Endothelium- dependent vasodilatation was assessed by the autopeffused hindlimb model. In aortic tissue, the expression of endothelial nitric oxide synthase（eNOS） mRNA were analyzed. Results Compared with normal control group, endothelium-dependent vasodilatation and the level of serum NO in STZ - induced type Ⅰ diabetic SD rats （ SD-STZ）group were obviously decreased （ P 〈 0.05）. The expression of eNOS mRNA in aortic tissue was significantly downregulated （ P 〈 0.05）. Compared with SD-STZ group,endotheliumdependent vasodilatation and the level of serum NO in Atorvastatin administration （Ator-Ad） group were obviously elevated （ P 〈 0.05）. The expression of eNOS mRNA in aortic tissue was significantly upregulated （ P 〈 0.05）. Conclusion Low-dose atorvastatin leads to a substantial improvement of endothelium-dependent vasodilatation in STZ-indueed type Ⅰ diabetic rats, independently of cholesterol-lowering.