小檗碱对早期糖尿病肾病大鼠肾组织TGF-β1/SnoN表达失衡及其Smad信号通路的调控作用  

Regulatory effect of berberine on unbalanced expressions of renal tissue TGF-β1/SnoN and Smad signaling pathway in rats with early diabetic nephropathy

作　　者：刘圣[1] 余娜[1,2] 张小力[1,2] 陈象青[1] 唐丽琴[1] 

机构地区：[1]安徽医科大学附属省立医院,安徽合肥230001 [2]安徽中医学院药学院,安徽合肥230038

出　　处：《中国中药杂志》2012年第23期3604-3610,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81102864;81073109);安徽省科研计划项目(08020303074);安徽省自然科学基金项目(090413106)

摘　　要：目的:研究小檗碱(BBR)对糖尿病肾病(DN)大鼠肾组织TGF-β1/SnoN表达失衡及其Smad信号通路的调控作用,探讨BBR对DN大鼠早期肾脏损伤的作用及其可能机制。方法:以链脲佐菌素(STZ)复制早期DN大鼠模型,动物分为正常对照组、模型组、BBR低、中、高剂量(50,100,200 mg.kg-1)治疗组及阳性对照(依那普利1 mg.kg-1)治疗组,灌胃给药,每日1次,5周后检测大鼠空腹血糖(FBG)、尿素氮(BUN)、血肌酐(Scr)、24 h尿蛋白(24 h Upro)及24 h尿微量白蛋白(24 hUmAlb);光镜观察肾组织形态学的改变;免疫组织化学检测肾组织TGF-β1,SnoN,Smad2/3与Smad7蛋白表达;逆转录聚合酶链反应(RT-PCR)检测肾组织TGF-β1 mRNA表达。结果:与模型组比较,BBR各治疗组大鼠FBG,BUN,Scr,24 h Upro及24 hUmAlb水平显著降低;肾组织形态学异常改善;TGF-β1蛋白及mRNA和Smad2/3蛋白表达显著减少,SnoN和Smad7蛋白表达显著增加。结论:BBR可通过Smad信号通路来维持DN肾组织TGF-β1/SnoN表达的动态平衡,从而改善早期DN大鼠肾功能病变,延缓DN的发生与发展。Objective： To investigate the effect of berberine （BBR） on unbalanced expression of renal tissue TGF-fll/SnoN and Smad signal pathway in rats with early diabetic nephropathy （DN） , and discuss BBR＇s effect on DN rats with early diabetic ne- phropathy and its possible mechanism. Method： DN rat model were established by injecting streptozotocin （STZ）. The rats were di- vided into six groups： the control group, the model group, three BBR （50, 100, 200 mg · kg^-1） treatment groups and the enalapril treatment group. They were orally administered once a day for five weeks. The fasting blood glucose （ FBG）, blood urea nitrogen （ BUN）, serum creatinine （Scr）, urinary protein （24 h Upro） and urinary microalbumin （24 h UmAlb） were tested. The pathological changes in renal tissues were examined by optical microscopy. Immunohistochemical measures were used to detect the expressions of TGF-β1, SnoN, Smad2/3 and Smad7 protein, and RT-PCR was used to detect TGF-β1 mRNA in renal tissues. Result： Compared with the model group, BBR-treated groups showed significant decrease in FBG, BUN, Scr, 24 h Upro, 24 h UmAlb, TGF-β1 protein, mRNA and Smad2/3 protein, abnormal morphological improvement in renal tissues, and notable increase in the expressions of SnoN and Smad7 protein. Conclusion： BBR can maintain the dynamic balance in TGF-β1/SnoN expression in renal tissues through Smad signaling pathway, so as to mitigate renal functional disorder in DN rats and delay DN and its development.

关 键 词：小檗碱 糖尿病肾病 TGF-Β1 SNON SMAD信号通路 

分 类 号：R285.5[医药卫生—中药学]