健脾清化方对肾纤维化大鼠肾功能、蛋白尿及肾组织Col-IV表达的影响
Impact of Jianpi Qinghua Fang on Renal Function, Proteinuria and Kidney Col-IV Expression in Rats with Renal Fibrosis
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摘要: 目的 探讨健脾清化方对肾切除联合阿霉素诱导局灶节段性肾小球硬化模型大鼠肾功能、蛋白尿及肾组织IV型胶原(Col-IV)表达的影响。方法 建立单侧肾切除合并阿霉素3 mg/kg尾静脉2次注射大鼠肾硬化模型,分别予以健脾清化方、健脾清化方拆方(益气健脾方及清热化湿方)、尿毒清颗粒干预8周。测定用药后各组肾功能及24 h尿蛋白定量,实时荧光定量PCR法测定肾组织Col-IV表达水平。结果 模型组与空白组及假手术组相比,血清肌酐、尿素氮、24 h尿蛋白定量及肾组织Col-IV表达水平均明显升高(P<0.01)。与模型组相比,健脾清化方组血清肌酐、尿素氮、24 h尿蛋白定量及肾组织Col-IV表达水平均明显下降(P<0.01),清热化湿方组血清肌酐及肾组织Col-IV表达水平明显下降(P<0.01),尿素氮降低(P<0.05),尿毒清组尿素氮及肾组织Col-IV表达水平明显下降(P<0.01),血清肌酐、24 h尿蛋白定量降低(P<0.05),益气健脾方组各项指标均无明显下降(P>0.05)。结论 健脾清化方能下调肾组织IV型胶原的表达,从而抑制细胞外基质的积聚和肾小球系膜增殖,发挥抗肾纤维化和保护残存肾功能的效用。其拆方清热化湿方在改善肾功能和肾纤维化方面的疗效与健脾清化方接近,提示清热化湿类药物是健脾清化方抗肾纤维化的关键。Abstract: OBJECTIVE To investigate the impact of Jianpi Qinghua Fang on renal function, proteinuria and kidney Col-IV expression in focal segmental glomerulosclerosis rats induced by nephrectomy combined with adriamycin. METHODS The model of focal segmental glomerulosclerosis was prepared by the unilateral nephrectomy and the two injection of adriamycin in caudal vein of rat at a dose of 3 mg/kg. The gastric infusion with Jianpi Qinghua Fang, the disassembled prescription of Jianpi Qinghua Fang and Niaoduqing Capsule were administered separately for 8 weeks. The renal function and 24 h proteinuria were determined. The expression of Kidney Col-IV was determined by Real-Time Q-PCR. RESULTS Compared with control group and sham operation group, levels of SCr, BUN, 24 h proteinuria and kidney Col-IV expression in animals of model group were significantly higher (P<0.01). Compared with model group, in the group with Jianpi Qinghua Fang, levels of SCr, BUN, 24 h proteinuria and kidney Col-IV expression decreased significantly (P<0.01). Compared with model group, in the group with Qingre Huashi prescription, level of BUN decreased (P<0.05), while levels of SCr and kidney Col-IV expression decreased significantly (P<0.01). Compared with model group, in the group with Niaoduqing Capsule, levels of SCr and 24 h proteinuria decreased (P<0.05) while levels of BUN and kidney Col-IV expression decreased significantly (P<0.01). Compared with model group, in the group with Jianpi Yiqi prescription, levels of SCr, BUN, 24 h proteinuria and kidney Col-IV expression unchanged (P>0.05). CONCLUSION Jianpi Qinghua Decoction could inhibit the accumulation of extracellular matrix and the proliferation of glomerular mesangium by lowering the expression of Col-IV in kidney tissue.Therefore,the renal fibrosis was relieved by Jianpi Qinghua Decoction,and the residual renal function was protected.The disassembled prescription Qingre Huashi prescription has the close curative effect in improving the renal function and renal fibrosis,prompting herbs of clearing heat and removing dampness is the key of Jianpi Qinghua Decoction against renal fibrosis.