α-硫辛酸抑制高脂饮食对糖尿病大鼠心肌氧化应激的实验研究

Study of the Inhibition Effect of α-lipoic Acid on Myocardial Oxidative Stress in Diabetic Rats with High Fat Diet

目的观察α-硫辛酸(ALA)对高脂饮食饲养糖尿病大鼠心肌氧化应激的影响。方法 SD大鼠分为对照组(N组)、糖尿病组(D组)、高脂饮食组(H组)和α-硫辛酸组(L组),每组20只,后三组用小剂量链脲佐菌素制备糖尿病大鼠模型。N组及D组以普通饲料喂养,其余二组以高脂饲料喂养,L组给予ALA治疗12周。12周后测血糖、血脂水平,用黄嘌呤氧化酶法、硫代巴比妥酸比色法及Western blot方法分别检测心肌超氧化物歧化酶(SOD)、丙二醛(MDA)及核因子相关因子2(Nrf2)、血红素氧化酶-1(HO-1)表达情况。结果 (1)与N组比较,D组、H组及L组心肌SOD活性显著下降,组间比较差异有统计学意义(P<0.01),H组SOD活性较D组下降(P<0.01),L组SOD活性较H组升高,但低于D组,组间比较差异有统计学意义(P<0.01);(2)与N组比较,D组、H组及L组心肌MDA水平明显升高,组间比较差异有统计学意义(P<0.01),H组MDA水平较D组升高(P<0.01),L组MDA水平较H组降低,但高于D组,组间比较差异有统计学意义(P<0.01);(3)与N组比较,D组、H组及L组心肌Nrf2、HO-1表达增加,组间比较差异有统计学意义(P<0.01),H组Nrf2、HO-1表达高于D组(P<0.01),L组Nrf2、HO-1表达较H组升高,组间比较差异有统计学意义(P<0.01)。结论ALA可显著抑制高脂饮食诱导糖尿病大鼠心肌氧化应激,对糖尿病心肌病具有保护作用。

Objective To observe the effect of α-lipoic acid（ ALA） on myocardial oxidative stress in diabetic rats with high fat diet.Methods SD rats were divided into control group（ group N）,diabetic group（ group D）,high-fat diet group（ H group）and α-lipoic acid（ L group）,each group had 20 rats,and the latter three groups were prepared for diabetic rat model by small dose of streptozotocin.Group N and group D were fed with ordinary diet,the other two groups were fed with high fat diet,and group L was treated with ALA for 12 weeks.After 12 weeks,the levels of blood glucose and blood lipids were measured.The expressions of superoxide dismutase（ SOD）,malondialdehyde（ MDA）,nuclear factor related factor 2（ Nrf2） and heme oxygenase-1（ HO-1） of myocardium were detected by xanthine oxidase method,thiobarbituric acid colorimetry method and Western blot method respectively.Results（1）Compared with group N,the myocardial SOD activity in group D,H and L decreased significantly,the difference between groups was statistically significant（ P〈0. 01）,SOD activity in H group was lower than that in D group（ P〈0. 01）,and the SOD activity in L group was higher than that in group H,but it was lower than that in group D,the difference between groups was statistically significant（ P〈0. 01）.（2）Compared with group N,the myocardial MDA level in group D,H and L increased significantly,the difference between groups was statistically significant（ P〈0. 01）,MDA level in H group was higher than that in D group（ P〈0. 01）,and the MDA level in L group was lower than that in group H,but it was higher than that in group D,the difference between groups was statistically significant（ P〈0. 01）.（3）Compared with group N,the myocardial Nrf2、HO-1 expression in group D,H and L increased,the difference between groups was statistically significant（ P〈0. 01）,Nrf2、HO-1 expression in H group was higher than that in D group（ P〈0. 01）,and the Nrf2、HO-1 expression in L group was higher than that in group H,the difference between groups was statistically significant（ P〈0. 01）.Conclusion ALA can significantly inhibit the oxidative stress in the myocardium of diabetic rats with high fat diet,and it has protective effect on diabetic cardiomyopathy.