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.
出处
《中国中药杂志》
CAS
CSCD
北大核心
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)
