摘要
目的研究环孢素A(CsA)对大鼠肺纤维化的干预作用及TGF-β1/Smad3信号转导通路的作用机制。方法54只SD大鼠随机分为对照组、模型组和干预组。模型组、干预组经气管内注入博莱霉素(BLM,5 mg/kg)诱导肺纤维化模型,干预组次日CsA灌胃进行干预,对照组用生理盐水代替。各组注药后7天、14天和28天3个时间点分别处死6只大鼠。观察肺泡炎及肺纤维化程度;用免疫组织化学法检测转化生长因子β1(TGF-β1)和Smad3的表达;TUNEL检测28天各组大鼠肺组织细胞凋亡情况。结果对照组肺泡结构正常,模型组7天时以肺泡炎改变为主,14天时肺泡炎较前有所减轻,28天时以广泛性肺纤维化为主。干预组病理改变与模型组有同一规律,但肺泡炎和肺纤维化程度都轻于模型组。干预组各时间点TGF-β1和Smad3表达明显低于模型组(P<0.05),28天时大鼠肺组织中细胞凋亡指数干预组明显低于模型组。结论环孢素A可下调博莱霉素致肺纤维化大鼠肺组织TGF-β1/Smad3介导的细胞内信号转导途径,减少肺组织上皮细胞的凋亡,最终改善肺间质纤维化。
Objective To study, the effect of cyclosporin A （CsA） on bleomycm - induced pulmonary fibrosis in rats and its possible mechanism. Methods Forty - two Sprague Dawley （SD）rats were randomly divided into three groups ： normal control group （ C group）, bleomycin group （ B group） and cyclosporin A group （ T group）. Group B and group T were induced to produce pulmonary fibrosis with bleomycin endotracheally. Group T were treated with CsA daily from the next day of received bleomycin. While group B was given with normal saline instead. Six rats were killed on 7th, 14th and 28th day. The hydroxyprolline of pulmonary homogenate were measured for evaluation of the degree of pulmonary fibrosis. inununohistochemical method was performed to investigate the change of TGF -β1 land Slnad3 protein. TUNEL was applied to detect cell apoptosis. Results The lung of group C had no change on every, point, but that of group B showed acute inflammation on 7th day. Alveolitis relieved on the 14d. alveolar interval and part of alveolar spacearea occupied by collagen and fibrin on the 28d. Group T has the same tendency as group B;but the degree of alveolitis and pulmonary fibrosis decreased. Compared to group B, the expression of TGF-β1,Smad3 was decreased significantly in group T,so did the index of lung cells apoptosis.Conclusion CsA alleviates bleomycin induced pulmonary fibrosis in rats by downregulating the expression of TGF - β1 and the index of lung cells apoptosis . The probable mechanism was to intervene with the TGF - β1/Smad3 sig- nal pathway.
出处
《南华大学学报（医学版）》
2008年第1期25-28,共4页
Journal of Nanhua University(Medical Edition)
