CAJ | 학술논문

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。
목적：관찰혈관긴장태전화매억제약( ACEI)패나보리화곡니사특시부통과억제류양환단백( Trx)이산생항당뇨병신병( DN)양화응격효응。방법웅성SD대서40지，수궤분위정상대조조、모형대조조、곡니사특조、패나보리조，매조10지。정상대조조급여상규사료위양；모형대조조、곡니사특조、패나보리조급여고당고지음식조당뇨병신병모형。조모성공후，모형대조조여보통음식위양；곡니사특조여보통음식위양급곡니사특400 mg??kg－1??d－1，관위12주；패나보리조여보통음식위양급패나보리10 mg??kg－1??d－1，관위12주。관찰각조대서24 h뇨단백정량、혈당、혈뇨소담、혈기항급신장병리적변화，응용Western-blot측정Trx적함량。결과패나보리조화곡니사특조여모형대조조비교혈당、뇨단백、기항、뇨소담、신소구경화지수、신중/체질량명현하강，차이유통계학의의(균P<0.05)，패나보리조화곡니사특조간차이무통계학의의( P>0.05)。곡니사특여패나보리균유효감경신장병리변화，병능상조당뇨병신병대서신조직중Trx적표체。패나보리조Trx수평승고교곡니사특조경현저。결론곡니사특화패나보리균구유항당뇨병신병양화응격효응，이패나보리교곡니사특경현저，기궤제제항섬유화외，환능현저제고Trx적표체，종이억제양화응격반응，연완당뇨병신병적진전。
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.