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目的:探讨中药抗纤灵方对大鼠单侧输尿管结扎(UUO)所致肾纤维化的防治作用及机制。方法:用单侧输尿管结扎术建立大鼠肾纤维化模型,动态观察4周。治疗组以抗纤灵方在造模的同时开始灌胃,1次/d,共4周。治疗的第2周末检测BUN、Scr含量等指标,观察肾功能变化;第4周末采用HE染色、丽春红染色观察肾组织病理变化和胶原纤维沉积变化;采用RT-PCR法观察梗阻肾皮质C-Met、HGF、Erk1mRNA表达。结果:模型组大鼠BUN、Scr明显升高;肾小管和间质的结构基本消失,呈现弥漫的细胞增殖;肾间质胶原纤维增生和大量炎细胞浸润;肾组织C-Met mRNA表达显著上调,而HGF mRNA水平显著下调。中药抗纤灵方治疗组肾脏炎性细胞浸润及间质损伤均轻于模型组;BUN含量显著降低,Scr含量趋向正常;肾组织C-Met mRNA表达明显减少,HGF mRNA水平明显上调。ERK总基因水平的表达在假手术组、模型组及中药治疗组之间比较无明显差异。结论:抗纤灵方可能与抑制肾组织C-Met mRNA表达并增加抗肾纤维化的细胞因子HGF mRNA表达来改善大鼠梗阻性肾间质纤维化及肾功能有关。
OBJECTIVE: To investigate the preventive and therapeutic effects and mechanisms of traditional Chinese medicine Qianshen Lingfang on renal fibrosis induced by unilateral ureteral ligation (UUO) in rats. METHODS: Rat renal fibrosis model was established by unilateral ureteral ligation and dynamically observed for 4 weeks. The treatment group began to gavage at the same time as the anti-fibrostimide formula, once/d for 4 weeks. At the second weekend of treatment, BUN and Scr content were measured to observe the change of renal function. At the end of the 4th week, renal pathological changes and deposition of collagen fibers were observed by HE staining and Ponceau red staining. Obstruction of renal cortex was observed by RT-PCR. -Met, HGF, Erk1 mRNA expression. RESULTS: BUN and Scr were significantly elevated in the model group; the structure of the renal tubules and interstitium disappeared, showing diffuse cell proliferation; collagen fibrosis in the renal interstitium and infiltration of numerous inflammatory cells; and the expression of C-Met mRNA in the renal tissue was significantly upregulated. While HGF mRNA levels were significantly downregulated. The inflammatory cell infiltration and interstitial injury of kidney in the treatment group of Kangxianlingling were all lighter than those in the model group; the content of BUN was significantly decreased, the content of Scr tended to be normal, the expression of C-Met mRNA in the kidney was significantly decreased, and the mRNA level of HGF was significantly increased. There was no significant difference in the expression of ERK total gene levels between the sham group, the model group and the Chinese medicine treatment group. Conclusion: Kangxianlingfang may be related to inhibiting the expression of C-Met mRNA in renal tissue and increasing the expression of cytokine HGF mRNA against renal fibrosis to improve obstructive renal interstitial fibrosis and renal function in rats.