Abstract：
OBJECTIVE: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient\'s quality of life. TGF-β1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-β1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-β1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-β1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent.
METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-β1 with or without TGF-β1 inhibitor P144.
RESULTS: The serum level of IL-1β and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-β1, and obviously decreased when treated with P144.
CONCLUSIONS: TGF-β1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-β1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.
METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-β1 with or without TGF-β1 inhibitor P144.
RESULTS: The serum level of IL-1β and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-β1, and obviously decreased when treated with P144.
CONCLUSIONS: TGF-β1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-β1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.
摘要：
目的：食管再狭窄是食管支架置入术后的严重并发症，影响支架植入术的临床预后和患者的生活质量。TGF-β1/Smads信号通路在皮肤创伤后嗜酸性粒细胞性食管炎的发生发展和瘢痕修复中起重要作用。然而,TGF-β1/Smads在食管支架置入后食管再狭窄发展中的作用尚不清楚.我们的研究旨在探讨TGF-β1/Smads是否在食管支架术后再狭窄的发生发展中起重要作用。以及外源性TGF-β1抑制剂补充是否可以改善食管支架术后的食管再狭窄。
方法：建立大鼠食管支架置入后再狭窄模型，并通过免疫化学（IHC）测定TGF-β1/Smads信号通路的表达水平和成纤维细胞活化的相关标志物，Western印迹和实时qPCR。当暴露于有或没有TGF-β1抑制剂P144的rhTGF-β1时，食管成纤维细胞中的所有指标也被确定。
结果：支架组血清IL-1β和TNFα水平较空白对照组明显升高，用P144治疗时明显改善。支架组TGF-β1/Smads信号通路及成纤维细胞活化的相关标志物较空白对照组明显增多,用P144治疗时明显改善。当暴露于rhTGF-β1时，所有指标均显着增加，而当P144处理时，所有指标均显着降低。
结论：TGF-β1抑制剂P144可通过抑制TGF-β1/Smads信号通路下调成纤维细胞活化相关标志物的表达水平，从而保护食管支架术后良性再狭窄。并可作为食管支架置入术后良性再狭窄的新疗法。
方法：建立大鼠食管支架置入后再狭窄模型，并通过免疫化学（IHC）测定TGF-β1/Smads信号通路的表达水平和成纤维细胞活化的相关标志物，Western印迹和实时qPCR。当暴露于有或没有TGF-β1抑制剂P144的rhTGF-β1时，食管成纤维细胞中的所有指标也被确定。
结果：支架组血清IL-1β和TNFα水平较空白对照组明显升高，用P144治疗时明显改善。支架组TGF-β1/Smads信号通路及成纤维细胞活化的相关标志物较空白对照组明显增多,用P144治疗时明显改善。当暴露于rhTGF-β1时，所有指标均显着增加，而当P144处理时，所有指标均显着降低。
结论：TGF-β1抑制剂P144可通过抑制TGF-β1/Smads信号通路下调成纤维细胞活化相关标志物的表达水平，从而保护食管支架术后良性再狭窄。并可作为食管支架置入术后良性再狭窄的新疗法。
