牛蒡子总木脂素对自发性糖尿病大鼠肾脏病变的影响

Effects of total lignan from Fructus Arctii on kidney disease in spontaneous hyperglycemia rats

目的观察牛蒡子总木脂素对自发性糖尿病大鼠(GK大鼠)肾脏病变的影响。方法 20只GK大鼠造模成功后随机分为模型组和牛蒡子总木脂素组(300 mg·kg^(-1),ig,2次·d-1),同时采用10只同龄Wistar大鼠作为正常组。给药期间观察大鼠生长状况,每周监测体重。给药12 wk末,测定肾脏肥大指数、血尿素氮(BUN)、血肌酐(SCr)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、尿蛋白和尿微量白蛋白。并观察各组肾脏病变状况,采用Western blot法检测肾皮质中转化生长因子β_1(TGF-β1)和结缔组织生长因子(CTGF)的表达水平。结果至实验结束,3组动物的体重增长无显著差异。总木脂素组肾脏肥大指数为(3.62±0.10)×10^(-3),低于模型组[(4.50±0.49)×10^(-3),P<0.05],与正常组无显著差异[(3.27±0.31)×10^(-3),P>0.05],光镜下总木脂素组肾脏病理改变较模型组轻微。总木脂素组大鼠SCr、BUN、HbA_(1c)、FBG及尿微量白蛋白水平均低于模型组(P<0.01),其中SCr、BUN、HbA_(1c)及尿微量白蛋白水平与正常组无显著差异(P>0.05)。总木脂素组肾皮质中TGF-β_1和CTGF蛋白表达水平(22.98±5.08和21.30±2.21)低于模型组(26.58±2.35和24.93±4.26,P<0.05),TGF-β_1水平接近正常组(22.32±2.49,P>0.05),CTGF仍显著高于正常组(17.18±3.64,P<0.01)。结论牛蒡子总木脂素可以减轻GK大鼠肾脏病理改变,改善肾脏功能,可能与抑制肾脏中TGF-β_1和CTGF的表达有关。

AIM To investigate the effects of total lignan from Fructus Arctii （TLFA） on kidney disease in Goto-Kakizaki （GK） rats. METHODS Twenty male GK rats were randomly divided into model group and TLFA group （300 mg-kg-1, ig, twice a day） after the model of hyperglycemic was established. Ten Wistar rats of the same age were set as normal group. Body weights of the rats were weighed every week during the experiment. After 12 weeks, biochemical parameters of blood and urine, the weigh ratio of kidney to body were measured. Microscopic features of the kidneys were evaluated by HE staining. The expressions of transforming growth factor beta 1 （TGF-β1） and connective tissue growth factor （CTGF） in renal cortex of the rats were detected by Western blot. RESULTS At the end of the experiment, there was no significant difference in weight growth of the rats of 3 groups. The weigh ratio of kidney to body of TLFA group （ （3.62 ± 0.10） × 10^-3） was significantly lower than that of the model group （ （4.50 ± 0.49） × 10^-3, P 〈 0.05）, but had no differences with that of the normal group （（3.27 ± 0.31） × 10^-3, P 〉 0.05）. Compared with the model group, the Scr, BUN, HbA1c, fast blood glucose and urinary albumin of the TLFA group were reduced significantly （P 〈 0.01 ） , pathologic manifestations of kidney also improved in the TLFA group. The expressions of TGF-β1 and CTGF in renal cortex were down-regulated in the TLFA group too. CONCLUSION TLFA could significantly lighten the pathological changes of kidney, improve renal function in GK rats, which might be associated with inhibiting the expression of TGF-β1 and CTGF in kidney.