转化生长因子-β_1在新生大鼠高浓度氧致肺损伤中的作用研究

Effect of TGF-β_1 on hyperoxic lung injury in neonatal rats

目的观察应用外源性抗转化生长因子-β1(TGF-β1)抗体作用下TGF-β1在新生鼠高浓度氧(高氧,>95%O2)致肺损伤的表达。方法将足月SD新生大鼠随机分为3组:空气对照组(Ⅰ组),高氧(>95%O2)组(Ⅱ组),高氧(>95%O2)+抗TGF-β1抗体0.4mg/kg组(Ⅲ组)。每组20只,观察及检测高氧暴露3、7、14和28d时各组动物肺组织病理改变、TGF-β1免疫组织化学染色。结果Ⅱ组3和7d时表现为明显的急性炎症改变,肺组织水肿、渗出、出血、肺泡间隔轻度增厚,14d时急性炎症减轻,而肺组织中TGF-β1表达呈强阳性;28d时出现明显的胶原沉积,形成纤维化;Ⅲ组3和7d时仍有轻度炎症反应,14和28d无明显成纤维细胞增生及胶原生成,未形成肺纤维化,Ⅲ组各时相点TGF-β1的表达明显减弱,与Ⅰ组比较差异无统计学意义。结论新生鼠持续吸入高氧后可导致急、慢性肺损伤。高氧暴露可刺激肺部产生过量的TGF-β1,提示TGF-β1在肺纤维化过程中起重要作用;高氧暴露时给予外源性抗TGF-β1抗体对新生鼠高氧暴露有明显保护作用,可减轻高氧急性肺损伤,能有效阻断高氧肺纤维化损伤的发生、发展,从而减轻肺纤维化损伤。

Objectives To observe the expression level of TGF-β1 in the lung of neonatal rats exposed to the hyperoxia inhalation to the role of ectogenesis anti-TGF-β1 on hyperoxic lung fibrosis. Methods Sixty clean Sprague-Dawley（SD） rats which were less than 1Zh old were enrolled in this study. The neonatal rats were divided into 3 groups randomly：normal air control group（group Ⅰ） ; 〉95%O2 control group（group Ⅱ ） ; 〉95%O2 ＋anti-TGF-β1l 0.4mg/kg （groupⅢ）. Group Ⅰ were placed in the room air. Group Ⅱ and Ⅲ were placed into oxygen cabins and were exposed to 〉95% O2 for 3d,at same time,neonatal rats had nebulization therapy with anti-TGF-β1 3d,oncee everyday. After at 3d, 7d, 14d and 28d of exposure to high concentration oxygen（U2 〉95%）, the changes of the pathologic alteration in lung were measured,and the expression levels of TGF-β1 were measured by immunohistochemis- try. Results At hyperoxia 3d and 7 d,the lung of group Ⅱ neonatal rats were acute inflammations. Microvessel hyperemia,edema, inflammatory cell infiltration, hemorrhage were found by using light microscope and transmission electron microscope. But the expression level of TGF-β1 obviously increased in lung of group Ⅱ. At hyperoxia 14d,that edema,inflammatory cell infiltration,hemorrhage reduced,made fibrosis changed in lung,the expression level of TGF-β1 were the most strong in lung. At hyperoxia 28d there were obvious inflammation and wider alveolus alternation than other groups and there were strong express of TGF-β1 in Ⅱ group. Group Ⅰ were not obvious inflammation than other groups and there were not the expression level of TGF-β1 in lung. There were no fibrosis at 14--28d. There were no significant fibrosis increased at hyperoxia 14--28d in group Ⅲ. Campared these three groups, the expression level of TGF-β1 had no increase at hyperoxia 14--28d in group I and In ,they had a low level. Lung structures had no disorder,no ECM and lung fibrosis was found by using light microscope and transmission electron microscope. Conclusion Hyperoxia can cause acute or chronic lung injury. Hyperoxia can obviously increase the expression level of TGF-β1, cause lung constitutions disorder and lung fibrosis,which indicates TGF-β1 has key role in fibrosis. Anti-TGF-β1 inhibites the ALI and lung fibrosis.