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Pirfenidone: A novel anti-fibrotic agent and progressive chronic allograft rejection.

机译:吡非尼酮:一种新型抗纤维化药和进行性慢性同种异体移植排斥反应。

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摘要

In our established model of heterotopic tracheal transplantation, at day 28 following transplantation, obliteration of the lumen is observed, which is histologically similar to that seen in Obliterative Bronchiolitis (OB). Pirfenidone (Pir) is a novel anti-fibrotic agent that causes no immunosuppression, but does downregulate the production of TGF-beta and collagen in vitro. We hypothesized that when used in this in vivo model, that Pir may alter the observed luminal fibrosis and obliteration.METHODS: The treatment groups were: CSA, Pir and CSA, Pir only (n=6 each). Luminal supernatants and tissue were obtained from these groups at day 28. H&E staining was completed, as well as MTS proliferation assays, and TGF-beta ELISA on the fluids.RESULTS: The CSA-Pir combined treatment group was the least fibrogenic in vitro (p<0.001). The TGF-beta levels were elevated in all groups (range 203-372 pg/ml). The H&E staining revealed that the luminal obliteration was less organized in the combined CSA-Pir group.CONCLUSIONS: Our study shows that the combination of CSA-Pir results in a less fibrogenic luminal fluid and a less dense fibrous luminal plug. Pir should be further studied in obliterative airways disease (OAD).
机译:在我们建立的异位气管移植模型中,移植后第28天观察到管腔闭塞,其组织学与闭塞性细支气管炎(OB)相似。吡非尼酮(Pir)是一种新型抗纤维化剂,它不会引起免疫抑制,但会在体外下调TGF-β和胶原蛋白的产生。我们假设在该体内模型中使用Pir可能会改变观察到的腔内纤维化和闭塞。方法:治疗组为:CSA,Pir和CSA,仅Pir(每个n = 6)。在第28天从这些组获得了发光的上清液和组织。完成了H&E染色以及液上的MTS增殖测定和TGF-βELISA。结果:CSA-Pir联合治疗组在体外的纤维化最少( p <0.001)。所有组的TGF-β水平均升高(范围为203-372 pg / ml)。 H&E染色显示,CSA-Pir联合治疗组的管腔闭塞组织较少。结论:我们的研究表明,CSA-Pir联合使用可减少纤维化的管腔液和密度较小的纤维状管腔堵塞。在闭塞性气道疾病(OAD)中应进一步研究Pir。

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