伊贝沙坦对糖尿病大鼠心脏的保护作用及抗氧化反应的机制探讨

Protective Effects of Irbesartan on Heart and Anti-oxidative Effects in Diabetic Rats

【目的】探讨血管紧张素Ⅱ受体拮抗剂伊贝沙坦对糖尿病大鼠心脏的保护作用及其相关机制。【方法】将30只Wistar大鼠随机分为正常对照组、糖尿病组和伊贝沙坦组3组,每组10只。造模后12周终止实验处死大鼠,取血、尿和心脏标本,测定尿量、体质量、心脏质量/体质量、血糖、糖化血红蛋白(HbA1c);测定血液和心脏组织的丙二醛(MDA)和超氧化物歧化酶(SOD)的活性;通过电镜观察心肌超微结构的变化。【结果】12周终止实验时糖尿病各组大鼠的尿量、心脏质量/体质量、血糖、HbA1c、血清和心脏组织的MDA水平均明显高于正常组,而体质量、红细胞和心脏组织的SOD活性明显低于正常组(P<0.05);伊贝沙坦组大鼠的血清和心脏组织的MDA水平明显低于糖尿病组,而SOD的活性高于糖尿病组(P<0.05)。糖尿病组大鼠的心肌细胞超微结构明显损伤,伊贝沙坦组大鼠的心脏组织超微结构损伤较轻。【结论】伊贝沙坦能减轻糖尿病大鼠心脏损害的进展,其机制可能与伊贝沙坦抑制糖尿病大鼠脂质过氧化反应和提高抗氧化能力有关。

[ Objective ] To investigate the protective effects of irbesartan on myocardium and its anti-oxidative stress mechanism in diabetic rats. [Methods] Thirty male Wistar rats were randomly divided into three groups： control group（n=10）, diabetic group（n=10）, irbesartan group（n=10）. At the end of 12 weeks, the rats were killed. Urine volume, body mass, heart mass/body weight, plasma glucose, glycosylated hemoglobin （HbA1c） were measured. Malondialdehyde （MDA） levels and superoxide dismutase （SOD） activity in serum or red blood cells and heart tissueS were tested. Myocardium was taken for electromicroscopy. [ReSults] Urine volume, heart mass/body mass, plasma glucose, HbA1C MDA levels of blood and heart tissue in diabetic rats were significantly greater than those of normal controls （P〈 0.05）. But body weight, SOD activity of blood and heart tissue in control group were higher than that of diahetic and irbesartan group. After 8 weeks of treatment, SOD activity of red blood cells and heart tissue in rats of irdesartan group were significantly higher than those of diabetic rats （P〈 0.05）. The injurieS of the myocardlum including sareomeres, mitochondria and microvascular endothelial cells were less in irbesartan group than that in diabetic group. [Conclusion] aIrbesartan could decrease the heart injury in diabetic rats. And the mechanisms might be that irbesartan can reduce the MDA levels and improve SOD activity in STZ-induced diabetic rats.