Liu Sheng, Yu Na, Zhang Xiao-Li, Chen Xiang-Qing, Tang Li-Qin
Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
Zhongguo Zhong Yao Za Zhi. 2012 Dec;37(23):3604-10.
To investigate the effect of berberine (BBR) on unbalanced expression of renal tissue TGF-beta1/SnoN and Smad signal pathway in rats with early diabetic nephropathy (DN), and discuss BBR's effect on DN rats with early diabetic nephropathy and its possible mechanism.
DN rat model were established by injecting streptozotocin (STZ). The rats were divided into six groups: the control group, the model group, three BBR (50, 100, 200 mg x 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-beta1, SnoN, Smad2/3 and Smad7 protein, and RT-PCR was used to detect TGF-beta1 mRNA in renal tissues.
Compared with the model group, BBR-treated groups showed significant decrease in FBG, BUN, Scr, 24 h Upro, 24 h UmAlb, TGF-beta1 protein, mRNA and Smad2/3 protein, abnormal morphological improvement in renal tissues, and notable increase in the expressions of SnoN and Smad7 protein.
BBR can maintain the dynamic balance in TGF-beta1/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.
探讨小檗碱(BBR)对早期糖尿病肾病(DN)大鼠肾组织TGF-β1/SnoN及Smad信号通路失衡表达的影响,探讨BBR对早期糖尿病肾病大鼠的作用及其可能机制。
通过注射链脲佐菌素(STZ)建立DN大鼠模型。将大鼠分为六组:对照组、模型组、三个BBR(50、100、200mg·kg⁻¹)治疗组和依那普利治疗组。每天灌胃给药一次,共五周。检测空腹血糖(FBG)、血尿素氮(BUN)、血清肌酐(Scr)、尿蛋白(24h Upro)和尿微量白蛋白(24h UmAlb)。用光镜检查肾组织的病理变化。采用免疫组化法检测TGF-β1、SnoN、Smad2/3和Smad7蛋白的表达,采用RT-PCR法检测肾组织中TGF-β1 mRNA的表达。
与模型组相比,BBR治疗组的FBG、BUN、Scr、24h Upro、24h UmAlb、TGF-β1蛋白、mRNA和Smad2/3蛋白显著降低,肾组织形态异常改善,SnoN和Smad7蛋白表达显著增加。
BBR可通过Smad信号通路维持肾组织中TGF-β1/SnoN表达的动态平衡,从而减轻DN大鼠的肾功能紊乱,延缓DN及其发展。