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目的探讨百令胶囊对小管间质纤维化大鼠小管上皮-间质转分化的干预作用。方法利用腺嘌呤诱导建立肾小管间质纤维化大鼠模型,实验SD大鼠随机分为模型组、干预组、对照组各30只,分别于实验第7周、12周、17周收获动物各10只,进行功能学和肾脏组织病理学检测和观察。利用免疫组织化学对骨形态发生蛋白-7(BMP-7)、转化生长因子-β1(TGF-β1)和α-平滑肌肌动蛋白(-αSMA)在肾小管间质纤维化大鼠中的表达变化进行动态观察及百令胶囊的干预影响。结果实验第7周模型组大鼠即表现出大量蛋白尿、小管损伤、间质的轻度纤维化和炎症细胞浸润(P<0.01);随病程进展,上述病变呈进行性加重(P<0.01)。百令胶囊干预组动物在实验第7周、12周功能学组织学的改善同实验组相比有明显差异(P<0.01),17周后二者无显著差异。免疫组织化学显示百令胶囊12周前能显著上调BMP-7的表达和降低-αSMA和TGF-β1在肾脏小管间质中的表达(P<0.01),12周后这种变化无差异。结论百令胶囊在发病早期通过有效干预上皮-间质转分化达到改善肾脏纤维化的作用,随着肾小管间质纤维化程度的加重,百令胶囊逐渐失去其阻断作用。
Objective To investigate the intervention effect of Bailing capsule on tubule interstitial-interstitial transdifferentiation in tubulointerstitial fibrosis rats. Methods Adenine-induced rat model of tubulointerstitial fibrosis was established. Experimental SD rats were randomly divided into model group, intervention group, and control group (n = 30). Animals were harvested at the 7th, 12th, and 17th week of experiment respectively. Ten rats were examined for functional and renal histopathology. Expression of bone morphogenetic protein-7 (BMP-7), transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (-αSMA) in rat tubulointerstitial fibrosis by immunohistochemistry Changes were observed dynamically and the influence of Bailing capsule intervention. Results In the 7th week of the experiment, the rats in the model group showed a large amount of proteinuria, tubule injury, mild interstitial fibrosis and inflammatory cell infiltration (P<0.01); with the progression of the disease, these lesions progressively aggravated (P<0.01). ). The improvement of functional histology of the animals in the Bailing capsule intervention group at the 7th and 12th weeks was significantly different from that of the experimental group (P<0.01). There was no significant difference between the two groups after 17 weeks. Immunohistochemistry showed that Bailing capsules could significantly up-regulate the expression of BMP-7 and decrease the expression of -αSMA and TGF-β1 in tubulointerstitium (P <0.01) 12 weeks ago, and there was no difference in this change after 12 weeks. Conclusion Bailing capsule gradually loses its blocking effect by effectively intervening in the epithelial-mesenchymal transdifferentiation to improve renal fibrosis in the early stage of the disease. With the increase of renal tubulointerstitial fibrosis, Bailing capsule gradually loses its blocking effect.