罗格列酮对2型糖尿病大鼠心肌NADPH氧化酶亚单位表达的影响

The effect of rosiglitazone to the expression of NADPH oxidase in the heart of type 2 diabetic rats

目的:探讨罗格列酮对2型糖尿病大鼠心肌p22phox和NOX4mRNA表达的影响,分析罗格列酮保护心脏的可能机制。方法:36只雄性Wistar大鼠,随机分为3组:健康对照组(A组,10只),糖尿病组(B组,13只)和罗格列酮治疗组(C组,13只),采用高糖高脂饮食小剂量链脲佐菌素(STZ)的方法诱导糖尿病模型。用免疫组织化学法检测心脏组织中CTGF和Cu-Zn-SOD的表达,用实时荧光定量PCR法测定心肌p22phox和NOX4 mRNA的表达。结果:糖尿病组(B组)大鼠大鼠心肌CTGF和NADPH氧化酶亚单位p22phox和NOX4 mRNA表达水平均较正常对照组(A组)显著升高(P<0.05),心肌Cu-Zn-SOD显著低于A组。罗格列酮治疗后,糖尿病大鼠(C组)心肌CTGF和NADPH氧化酶亚单位p22phox和NOX4mRNA表达水平显著降低(P<0.05),心肌Cu-Zn-SOD显著高于B组。结论:罗格列酮抑制2型糖尿病大鼠心肌NADPH氧化酶亚单位p22phox和NOX4 mRNA的过度表达,升高心肌Cu-Zn-SOD的表达水平,降低心重/体重(心脏肥大指数)和心肌CTGF表达,延缓糖尿病心肌病的进展,可能是其心脏保护作用机制之一。

Objective： To expore the effect of rosiglitazone to the expression of p22phox and NOX4 mRNA in heart of type 2 diabetic rats and to analysis the potential protective mechanisms of rosiglitazone on heart. Methods： 36 male Wistar rats were randomly divided into three groups： healthy control group （group A, n=10）, diabetic group （group B, n=13） and rosiglitazone group （group C, n =13）. Applying the method of high glucose and high fat diet low-dose streptozotocin （STZ） to induced diabetic model. Immunohistochemistry staining was used to detect the expression of CTGF and Cu-Zn-SOD in the heart of rats. Detecting the mRNA expression of myocardial p22phox and NOX4 by real-time PCR. Results： The mRNA expression of myocardial p22phox and NOX4 and the expression of myocardi al CTGF were significantly increased in group B than those in group A, while the expression of myocardial Cu-Zn-SOD was significantly decreased in group B than that in group A. After rosiglitazone treatment, the mRNA expression of myocardial p22phox and NOX4 and the expression of myocardial CTGF were significantly decreased in group C. The expression of myocardial Cu-Zn-SOD was significantly increased in group C than that in group B. Conclusion： Rosiglitazone inhibited the overexpression of myocardial p22phox and NOX4, increased the expression of myocardial Cu-Zn-SOD, and decreased the ratio of heart or body weight. （index of cardiac hypertrophy） and the expression of myocardial CTGF in type 2 diabetic rats, which resulted in the delay of the progression of diabetic cardiomyopathy, which may be one of the cardioprotective mechanisms of rosiglitazone.