健脾益肾丸对肾脏纤维化大鼠TGF-β1/Smads信号通路相关基因表达的研究

摘要

目的:研究健脾益肾丸对5/6肾切除大鼠模型肾损伤的改善作用,并分析探讨其可能存在的机制.方法:40只SD大鼠随机分为假手术组、模型对照组、健脾益肾丸低剂量组(2.06 g/kg·d-1)、健脾益肾丸高剂量组(10.89 g/kg·d-1)、培哚普利组(4 mg/kg·d-1),每组10只.造模4个月后开始给药,连续给药6周.6周后处死大鼠,留取血清,采用酶联免疫吸附试验法检测血肌酐(Scr)、尿素氮(BUN);采用实时荧光定量PCR法检测肾组织TGF-β1、Smad2、Smad3 mRNA基因表达.结果:健脾益肾丸不同剂量均可明显降低大鼠血清Scr、BUN水平(P<0.01/P<0.05),下调TGF-β1、Smad2、Smad3 mRNA基因表达(P<0.01);培哚普利作为西药阳性对照,可明显降低大鼠血清Scr、BUN水平(P<0.01/P<0.05),下调TGF-β1、Smad2、Smad3 mRNA基因表达(P<0.01).结论:健脾益肾丸能有效改善5/6肾切除慢性肾衰大鼠模型肾功能;其机制可能与下调TGF-β1、Smad2、Smad3水平,从而抑制过度激活的TGF-β1/Smads信号通路有关.%Objective: to study the improvement function of Jianpi Yishen Pill on renal injury of 5/6 nephrectomy in rats, and to explore the possible mechanism.Methods: 40 SD rats were randomly divided into sham operation group, control group, low dose of Jianpi Yishen Pill group (2.06 g/kg·d-1), high dose group (10.89 g/kg·d-1), and Perindopril group (4 mg/kg·d-1), 10 rats a group.4 months after models finished, administration began and it lasted for 6 weeks.The rats were then killed with serum taken.Enzyme-linked immunosorbent test was used to detect serum creatinine (Scr) and blood urea nitrogen (BUN), and real-time fluorescence quantification PCR to detect gene expressions of TGF-β1, Smad2, Smad3 and mRNA.Results: both high and low dose of Jianpi Yishen Pill could significantly decrease Scr and BUN (P<0.01/P<0.05) and lower TGF-β1, Smad2, Smad3 and mRNA expressions (P<0.01);Perindopril could significantly decrease Scr and BUN (P<0.01/P<0.05) and lower TGF-β1, Smad2, Smad3 and mRNA expressions (P<0.01).Conclusion: Jianpi Yishen Pill can effectively improve the renal function of 5/6 nephrectomy in rats with chronic renal failure, whose mechanism may be related to inhibiting the excessive activated TGF-β1/Smads signal path through lowering TGF-β1, Smad2 and Smad3.