贝那普利和曲尼司特抗糖尿病肾病氧化应激效应比较

Comparison of Effect on Antioxidative Stress Between Benezepril and Tranilast in Diabetic Nephropathy Rat

目的观察血管紧张肽转化酶抑制药(ACEI)贝那普利和曲尼司特是否通过抑制硫氧还蛋白(Trx)而产生抗糖尿病肾病(DN)氧化应激效应。方法雄性SD大鼠40只,随机分为正常对照组、模型对照组、曲尼司特组、贝那普利组,每组10只。正常对照组给予常规饲料喂养;模型对照组、曲尼司特组、贝那普利组给予高糖高脂饮食造糖尿病肾病模型。造模成功后,模型对照组予普通饮食喂养;曲尼司特组予普通饮食喂养及曲尼司特400 mg·kg-1·d-1,灌胃12周;贝那普利组予普通饮食喂养及贝那普利10 mg·kg-1·d-1,灌胃12周。观察各组大鼠24 h尿蛋白定量、血糖、血尿素氮、血肌酐及肾脏病理的变化,应用Western-blot测定Trx的含量。结果贝那普利组和曲尼司特组与模型对照组比较血糖、尿蛋白、肌酐、尿素氮、肾小球硬化指数、肾重/体质量明显下降,差异有统计学意义(均P<0.05),贝那普利组和曲尼司特组间差异无统计学意义(P>0.05)。曲尼司特与贝那普利均有效减轻肾脏病理变化,并能上调糖尿病肾病大鼠肾组织中Trx的表达。贝那普利组Trx水平升高较曲尼司特组更显著。结论曲尼司特和贝那普利均具有抗糖尿病肾病氧化应激效应,而贝那普利较曲尼司特更显著,其机制除抗纤维化外,还能显著提高Trx的表达,从而抑制氧化应激反应,延缓糖尿病肾病的进展。

Objective To investigate ACEI （ benazepril ） and tranilast exert renoprotective properties in diabetic nephropathy（ DN） through the inhibition of thioredoxin（ Trx） . Methods Forty male SD rats were randomly divided into normal control group,model control group,tranilast group and benazepril group （n=10 each）.Normal control group was fed with normal diet. Other groups were fed with high-glucose high-fat diet to make DN models. Rats in model control, tranilast, and benazepril groups were fed with normal diet,400 mg·kg-1·d-1 tranilast plus normal diet,and 10 mg·kg-1·d-1 benazepril plus normal diet,respectively,via oral gavage for 12 weeks.The 24-hour proteinuria,blood glucose（BG）,blood urea nitrogen （BUN）,serum creatinine （ Scr） and renal pathology changes were detected. Expression of Trx was measured by Western-blot. Results The 24 h urine protein, BG, BUN, Scr, kidney/body weight, and glomerular sclerosis index were significantly decreased in tranilast group and benazepril group,as compaired with model control group （ P〈0.05） ,but there was no statistical difference between the two drug groups （P〉0.05）.Both tranilast and benazepril can reduce renal pathological changes,and can increase the expression of Trx of DN rats, but benazepril had a more significant effect on increasing Trx expression. Conclusion Both tranilast and benazepril have renoprotective function in DN, and benazepril is more effective than tranilast in delaying the progression of diabetic nephropathy by increasing Trx expression and decreasomg oxidative stress.