肺ECM水凝胶抑制TGF-β1/Smad3通路减轻大鼠放射性肺纤维化  

Lung extracellular matrix hydrogel alleviating radiation induced pulmonary fibrosis in rats via inhibiting TGF-β1/Smad3 pathway

作　　者：吴鹏飞 但梦霞 邱立志[1] 弋可 王洪州 薛培丽[1] WU Peng-fei;DAN Meng-xia;QIU Li-zhi;YI Ke;WANG Hong-zhou;XUE Pei-li(Department of Respiratory and Critical Care Medicine,Sichuan Science City Hospital,Mianyang,Sichuan 621000,China)

机构地区：[1]四川省科学城医院呼吸与危重症医学科,四川绵阳621000

出　　处：《临床肺科杂志》2022年第6期833-837,共5页Journal of Clinical Pulmonary Medicine

基　　金：四川省医学青年创新课题(No.Q19005)。

摘　　要：目的探索肺ECM水凝胶是否抑制TGF-β1/smad3通路,减轻放射性肺纤维化。方法20 Gy照射制备大鼠放射性肺纤维化模型,将27只大鼠随机分为3组(n=9):Control组、IR+NS组、IR+ECM组;Control组无处理,其余两组造模,在造模后0.5h,IR+NS组气管内注射0.9%氯化钠500μl,IR+ECM组注射等量肺ECM水凝胶,第16周取材,Elisa法测血清TNF-α、IL-6、TGF-β1,左肺固定后做病理染色(HE、Masson),右肺深低温保存做western blot、羟脯氨酸检测。结果与IR+NS组比,IR+ECM组大鼠血清TNF-α、IL-6、TGF-β1水平下降(P<0.05),肺系数降低(P<0.05),HE及Masson染色显示肺泡炎及纤维化程度改善,肺组织羟脯氨酸含量下降(P<0.05),TGF-β1、Smad3、p-Smad3、α-SMA蛋白表达下降(P<0.05)。结论肺ECM水凝胶能减轻大鼠放射性肺纤维化,可能是通过抑制TGF-β1/Smad3信号通路实现的。Objective To investigate whether the lung extracellular matrix hydrogel could reduce radiation induced pulmonary fibrosis via inhibiting the TGF-β1/smad3 pathway.Methods RIPF model in rat was set by 20 Gy radiation.27 rats were randomly divided into 3 groups(n=9):the control group,the IR+NS group,and the IR+ECM group.The control group received no treatment.In the IR+ECM group,500μl of lung ECM hydrogel was injected into the trachea 0.5 h after modeling.The same amount of 0.9% sodium chloride was injected into the trachea in the IR+NS group.16 weeks after modeling,the levels of TNF-α,IL-6 and TGF-β1 in serum was measured by Elisa.The left lung was fixed for staining(HE,Masson),and the right lung was stored at-80℃ for western blot and hydroxyproline detection.Results Compared with the IR+NS group,the serum TNF-α,IL-6 and TGF-β1 levels decreased more obviously(P<0.05),and the lung coefficient shrank more obviously(P<0.05)in the IR+ECM group.HE and Masson staining showed that lung alveolitis and fibrosis improved.The amount of hydroxyproline in pulmonary decreased(P<0.05).The expression of TGF-β1,Smad3,p-Smad3 andα-SMA protein decreased(P<0.05).Conclusion Lung ECM hydrogel can reduce RIPF in rats,which may be achieved by inhibiting the TGF-β1/Smad3 signaling pathway.

关 键 词：肺ECM水凝胶 TGF-Β1 SMAD3 放射性肺纤维化 

分 类 号：R563[医药卫生—呼吸系统]