小檗碱对大鼠糖尿病早期肾脏转化生长因子-β_1的影响

Effects of Berberine on Renal Transforming Growth Factor-β_1 in Early Diabetic Rats

目的:研究小檗碱对糖尿病(DM)大鼠早期肾脏转化生长因子-β1(TGF-β1)的影响,探讨小檗碱对DM大鼠早期肾脏损伤的作用及其可能机制。方法:100只Wistar大鼠随机分为5组各20只,分别为正常组、模型组、治疗1、2、3组。将模型组及治疗1、23、组制成1-DM模型,对治疗1、2、3组分别采用卡托普利50 mg/kg、小檗碱9.375及28.125 mg/kg混合液灌胃。4周后检测各组大鼠尿量、尿微量白蛋白含量、体重及肾重/体重比值,用血糖、肌酐清除率及TGF-β1mRNA的表达观察肾脏的病理结构变化。结果:观察4周后,尿量、肾重/体重比值、尿微量白蛋白、肌酐清除率、肾小球系膜及基底膜相对面积、TGF-β1及其mRNA在肾组织的表达模型组均明显高于正常组(P<0.05);治疗1、2组均明显低于模型组(P<0.05),与正常组相近。治疗3组对以上指标有部分改善作用。结论:小檗碱能延缓DM大鼠早期肾脏结构和功能损害的进展,其机制可能与小檗碱影响DM大鼠肾组织TGF-β1的表达有关,其中以低剂量为最佳。

Objective： By investigating the effects of berberine on renal transforming growth factor- β1 （TGF-β1） in early diabetic rats, to explore the effects and possible mechanisms of berberine on early kidney injury of diabetic rats. Methods： Fifty adult male Wistar rats were randomly divided into 5 groups： normal group, diabetic group, captopril group, low dose （9. 375 mg/kg） berberine group and high dose （28. 125 mg/kg） berberine group （n=10 in each group）. At the end of 4th week, the rats were sacrificed. Urine volume was recorded and the ratio of kidney to body weight was calculated. Blood glucose, urine microalbumin and creatinine clearance rate were determined. Immunohistochemical method was used to detect the expression of TGF-β1. The changes in renal pathological structures were observed under a light microscope. Results： After treatment for 4 weeks, urine volume, the ratio of kidney to body weight, urine microalbumin, creatinine clearance rate, relative area of glornerular mesangium to glornerular basement membrane, the expression of TGF-β1 in diabetic rats were significantly higher than in normal group （P〈0. 05）. Those of captopril group and low dose berberine groups were significantly lower than in diabetic group （P〈0. 05）, however, there was no significant difference in comparison with those in normal group. In high dose berberine group, the above indexes were changed partly. Conclusion：Berberine could prevent the injury of renal structure and function in early diabetic rats. The mechanism might be related to the fact that berberine could affect the expression of TGF-β1 in renal tissue, especially the low dose of berberine.