益肾活血汤对5/6肾切除大鼠PCNA表达及细胞外基质的影响

目的探讨益肾活血汤对5／6肾切除肾衰竭大鼠的防治效果及其作用机制。方法采用5／6肾切除大鼠模型，设立正常组、模型组、中药益肾活血汤组与西药苯那普利组。检测各组术后6周、12周末24h尿蛋白，12周末血清尿素氮（BUN）、血清肌酐（SCr）、血清白蛋白（Alb）、血红蛋白（HB）水平，12周末光镜观察肾组织病理变化，免疫组化检测肾增殖细胞核抗原（PCNA），纤维连接蛋白（FN）表达，RT—PCR检测肾结缔组织生长因子（CTGF）和纤溶酶原激活物抑制物-1（PAI-1）表达。结果（1）模型组较正常组24h尿蛋白，血清BUN、SCr，肾小球系膜区面积、FN聚积、肾小球和小管间质PCNA表达，CTGFmRNA，PAI—1mRNA表达均显著升高（P〈0．05），中药组较模型组各指标均显著下降（P〈0．05）；（2）正常组、模型组、中药和西药组肾小球PCNA阳性细胞数分别为7．00±2．24，34．78±6．96，15．75±2．61，15．50±2．57。且各组肾小球PCNA表达与CTGF、PAI-1、FN、SCr均呈正相关。结论中药益肾活血汤能够延缓5／6肾切除大鼠慢性肾功能衰竭进展，其机制主要与抑制肾脏细胞增殖及其诱导的细胞因子过度表达和细胞外基质聚积有关。

Effects of Yishen Huoxue Decoction on Proliferating Cell Nuclear Antigen Expression and Extracellular Matrix in 5/6 Nephrectomized Rats

OBJECTIVE: To investigate the effects and mechanisms of Yishen Huoxue decoction (YHD) on chronic renal failure (CRF) rats induced by 5/6 nephrectomy. METHODS: The glomerulosclerosis model was established by 5/6 nephrectomy in rats. Experimental animals were allocated into the normal group, the model group, the YHD group and the benazepril group. Urine protein of 24 h (UP) at the 6th and 12th weekend after operation, blood urea nitrogen (BUN) and creatinine (SCr), albumin (Alb) and haemoglobin (HB) at the 12th weekend were measured, renal pathology changes were examined with light microscope, the expressions of proliferating cell nuclear antigen (PCNA) and fibronectin (Fn) were examined by immunohistochemistry and mRNA expressions of connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1) by RT-PCR at the 12th weekend. RESULTS: Compared with those in the normal group, the levels of UP, BUN and SCr, the area of glomerular mesangial matrix, the FN deposition, PCNA expression in glomeruli and tubular interstitium and mRNA expressions of CTGF and PAI-1 were all significantly higher in the model group (P < 0.05). All the above-mentioned indexes were lower in the YHD group than those in the model group (P < 0.05). PCNA positively expressed cells in glomeruli of the normal, model group, YHD group and benazepril group was 7.00 +/- 2.24,34.78 +/- 6.96,15.75 +/- 2.61 and 15.50 +/- 2.57 respectively, positively correlated to the expression of CTGF, PAI-1, FN and SCr level. CONCLUSION: YHD could delay the progression of CRF in 5/6 nephrectomized rats, and the mechanisms were mainly related to the inhibition on renal cell proliferation and it induced over-expression of cytokines, and accumulation of extracellular matrix.