阿霉素肾病大鼠肾小管间质损害及益气血祛风湿方的干预作用

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目的:探讨益气血祛风湿方对阿霉素肾病肾小管间质损伤的有效治疗作用,为临床应用提供实验室理论依据。方法:采用阿霉素一次性尾静脉注射诱导的肾病模型,造模2周后用益气血祛风湿方或黄芪当归水煎剂等干预治疗。实验于第6周末处死大鼠,留取肾脏。采用HE染色观察肾组织病理改变;RT-PCR测定肾组织中TGF-β1基因表达;采用免疫组化技术检测肾小管间质MCP-1、TGF-β1的蛋白表达。结果:肾脏病理结果显示,模型组大鼠肾小管上皮浊肿、严重的空泡变性;肾小管不同程度扩张;可见较多蛋白管型;肾间质出现小灶性~灶性炎细胞浸润和灶性纤维化。各治疗组大鼠肾小管扩张、浊肿及间质炎细胞浸润等病理改变均较模型组减轻,肾间质纤维化程度也显著低于模型组。模型组大鼠肾组织和小管间质TGF-β1表达均显著增多,MCP-1阳性表达也显著增加,各治疗组肾小管间质中的MCP-1、TGF-β1表达较模型组显著降低,益气血祛风湿方组作用显著优于芪归治疗组。结论:益气血祛风湿方可显著改善肾小管间质的炎症损伤和纤维化程度,机制可能与其显著降低肾小管间质炎症因子和促纤维化细胞因子表达的作用有关。 Objective: To explore the effective therapeutic effect of Yiqi Xue Qu Wei Decoction on adriamycin-induced nephropathy tubulointerstitial injury, and to provide a laboratory theoretical basis for clinical application. Methods: The model of nephropathy induced by doxorubicin injection was established. After 2 weeks of modeling, the patients were treated with Yiqixue Qufeng Decoction or Huangqi Danggui Decoction. The rats were sacrificed at the end of the 6th week, and the kidneys were collected. The pathological changes of renal tissue were observed by HE staining. The expression of TGF-β1 gene in renal tissue was detected by RT-PCR. The protein expression of MCP-1 and TGF-β1 in tubulointerstitium was detected by immunohistochemistry. Results: The results of renal pathology showed that the tubular epithelial cells of the model group were swollen, with severe vacuolar degeneration, different degree of tubular dilatation, more protein tube type, small focal and inflammatory cell infiltration and focal lesion in the renal interstitium Fibrosis. The pathological changes of tubulointerstitial, turbidity and interstitial inflammatory cells in rats in each treatment group were alleviated compared with those in model group, and the degree of renal interstitial fibrosis was also significantly lower than that in model group. Compared with model group, the expression of TGF-β1 in renal tubulointerstitial and tubulointerstitial of model group increased significantly and MCP-1 positive expression increased significantly. The expressions of MCP-1 and TGF-β1 in tubulointerstitial of model group decreased significantly, Yiqi Xue Qufeng group significantly better than Qigui treatment group. Conclusion: Yiqi Xue Qufeng Decoction can significantly improve the tubulointerstitial inflammatory injury and fibrosis, the mechanism may be related to its significant reduction of tubulointerstitial inflammatory cytokines and promote the role of fibrotic cytokines.
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