环孢素A对肺纤维化大鼠模型TGF-β1/Smad3表达的影响

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. The immunohistochemical method was performed to investigate the change of TGF-β1and Smad3 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 signal pathway.