不同配比大黄黄芪对CRF大鼠TGF-β1/HGF因子表达的干预研究  

Effect of Different Ratios of Rhubarb and Astragalus on Expressions of TGF-β1/HGF in Chronic Renal Failure Rats

作　　者：宫仁豪 涂祎珺 李海燕[1] 钟瑜萍 赖有勤 GONG Renhao;TU Yijun;LI Haiyan;ZHONG Yuping;LAI Youqin(Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong,China)

机构地区：[1]广州中医药大学中药学院

出　　处：《辽宁中医杂志》2018年第11期2365-2369,2370,2461,共7页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(81403122)

摘　　要：目的:研究不同配比后的大黄黄芪对慢性肾衰竭(CRF)大鼠的肾间质纤维化程度及相关因子表达水平的影响,分析可能的相关作用机制。方法:采用5/6肾切除法复制慢性肾衰竭大鼠模型,模型大鼠按24h尿蛋白(UPr)水平分级后随机分为假手术组、模型组、贝那普利组(5×10^-3g/kg)、大黄组(1.5g/kg)、黄芪组(3g/kg)、大黄黄芪1:1(3g/kg)、1:2(4.5g/kg)、1:4(7.5g/kg)和1:6组(10.5g/kg),连续灌胃5周后,检查大鼠体质量、残余肾重及肾脏系数的大小,HE染色后观察肾组织形态学变化,检测各组大鼠24hUPr、血清肌酐(SCr)、尿素氮(BUN)、TGF-β1(转化生长因子β1)、TGF-β1mRNA、HGF(肝细胞生长因子)和C-Met(肝细胞生长因子受体)的水平。结果:①12周后模型制备成功,模型组大鼠体质量显著下降,肾脏系数、24hUpr、Scr、Bun水平显著升高;②给药5周后,各给药组大鼠体质量明显恢复,24hUPr、Scr、BUN和TGF-β1水平显著下降,肾脏组织损伤程度得到明显改善;大黄组和大黄黄芪1:2、1:4组肾重显著降低,且大黄:黄芪1:4组肾脏系数下降明显;各药物治疗组(除贝那普利组)C-Met的表达水平显著升高;大黄黄芪1:2、1:4与1:6组的TGF-β1mRNA表达显著降低;大黄黄芪1:2、1:6组大鼠的HGF蛋白量显著提高;综合以大黄:黄芪1:2组改善作用最为显著。结论:大黄黄芪不同配比后可以有效恢复慢性肾衰竭大鼠体质量,抑制残肾的代偿性肥大,下调代谢毒素的水平,同时可以调整TGF-β1/HGF的平衡,减轻肾纤维化程度。且配比给药疗效优于单味药,大黄:黄芪1:2组改善效果最为明显。Objective:To study the effect of rhubarb and Astragalus on the degree of renal interstitial fibrosis and the expression of related factors in chronic renal failure(CRF)rats and analyze the possible mechanism of action.Methods:Rats of chronic renal failure were established by 5/6 nephrectomy and model rats were randomly divided into sham operation group,model group,benazepril group(5×10^-3 g/kg),rhubarb group(1.5 g/kg),Astragalus group(3 g/kg),rhubarb and Astragalus 1:1 group(3 g/kg),1:2 group(4.5 g/kg),1:4 group(7.5g/kg)and 1:6 group(10.5 g/kg),according to the level of 24 h urinary protein(UPr).After five weeks of continuous intragastric administration,we detected the body weights,residual kidney weights and kidney coefficients,observed the configuration of renal tissue by optical microscope after HE staining,detected the levels of 24 h urine protein(Upr),serum creatinine(SCR),Urea nitrogen(BUN),TGF-β1,TGF-β1mRNA,HGF and C-Met(hepatocyte growth factor receptor).Results:After 12 weeks,the model of chronic renal failure was successfully established.The body weight of the model group decreased significantly;the renal coefficient,24 h Upr,Scr and BUN were significantly increased.After 5 weeks of administration,the body weight of each administration group was significantly restored;24 h UPr,Scr,BUN and TGF-β1 were significantly decreased;the degree of renal tissue injury was improved significantly.The renal weights of rhubarb group,rhubarb and astragalus 1:2 group and 1:4 group were significantly decreased and the kidney coefficient of 1:4 group was significantly decreased.In addition to the benazepril group,the expression of C-Met in each administration group was significantly increased;the relative expressions of TGF-β1mRNA in rhubarb and Astragalus 1:2 group,1:4 group and 1:6 group were significantly decreased.The amount of HGF protein in rhubarb and astragalus 1:2 group and 1:6 groups was significantly increased;the effect of rhubarb and astragalus 1:2 group was the most significant.Conclusion:Different rati

关 键 词：慢性肾衰竭 大黄 黄芪 24h尿蛋白 TGF-Β1 HGF 代谢毒素 肾纤维化 

分 类 号：R692.5[医药卫生—泌尿科学]