黄连素对糖尿病肾损伤大鼠肾功能、氧化应激、肾脏醛糖还原酶的影响

目的观察黄连素对链脲佐菌素诱导的糖尿病肾损伤大鼠肾功能保护作用,并从抗氧化应激、抑制肾脏醛糖还原酶活性及其基因表达等方面探讨黄连素抗糖尿病大鼠肾损伤的作用机制。方法用腹腔注射链脲佐菌素方法复制糖尿病大鼠肾损伤模型。随机分为正常对照组、模型对照组、黄连素组,每组10只。黄连素经口灌胃200 mg.kg-1.d-1,每周给药6 d,共12 wk。比较各组大鼠血糖、肾脏肥大指数(肾重/体重)、尿素氮(BUN)、血肌酐(Cr)、24h尿蛋白(UP24)等肾功能相关指标,比较各组血清超氧化物歧化酶(SOD)活性、脂质过氧化代谢产物丙二醛(MDA)含量、肾组织醛糖还原酶(AR)活性及其基因表达的改变。结果模型组大鼠血糖维持在较高水平、肾脏肥大指数、BUN、Cr、UP24等较正常组明显升高(P<0.05),血清SOD活性低下,MDA含量增加(P<0.05),肾脏AR活性与其基因表达明显升高(P<0.05)。黄连素组与模型组相比,能明显降低血糖、有效控制体重下降、明显改善肾脏肥大指数、BUN、Cr、UP24等指标(P<0.05),血清SOD活性增强,同时MDA含量减少(P<0.05),肾脏AR活性降低及AR mRNA水平下调(P<0.05)。结论对糖尿病肾损伤大鼠,黄连素在调节血糖的同时,可能通过提高机体抗氧化能力、减少肾脏AR活性与基因表达以抑制多元醇通路的激活发挥其肾功能的保护作用。

Effects of berberine on renal function, oxidative stress and renal aldose reductase in rats with diabetic nephropathy

Aim To investigate the protective effect of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy(DN).Methods Diabetes was induced by intraperitonal injection with streptozotocin(STZ) in male Wistar rats.The rats were randomly divided into normal group,model group and berberine group(n=10).Berberine(200 mg·kg1·d-1) was orally given to the rats in berberine group for 12 weeks.The fasting blood glucose(FBG),blood urea nitrogen(BUN),serum creatinine(Cr) and urine protein 24 h(UP 24 h) were measured using the commercially available kits.Meanwhile,superoxide dismutase(SOD) activity,malondialdehyde(MDA) content in serum,aldose reductase(AR) activity and AR gene expression in kidney were detected by different methods.Results FBG,kidney weight/body weight(KW/BW),BUN,Cr and UP 24 h were significantly increased in model group compared with normal group(P<0.05).Serum SOD activity was significantly decreased,and MDA content was increased in model group compared with normal group(P<0.05).Renal AR activity and its gene expression were enhanced obviously in model group compared with normal group(P<0.05).The treatment of berberine significantly ameliorated the above indices including FBG,body weight,KW/BW,BUN,Cr and UP 24 h compared with model group(P<0.05).Berberine significantly increased SOD activity and decreased MDA content in serum compared with those in model group(P<0.05).AR activity as well as its mRNA expression in kidney was markedly decreased in berberine group compared with model group(P<0.05).Conclusions These results suggested that berberine could ameliorate renal dysfunction in rats with DN through blood glucose control,reduction of oxidative stress,and inhibition of the activation of polyol pathway.