辛伐他汀对大鼠肺成纤维细胞的影响观察

目的 :探讨辛伐他汀 (Sim)对大鼠肺纤维化阶段肺成纤维细胞 (LFb)增殖和胶原合成的影响及其机制。方法 :肺纤维化 1周组肺泡巨噬细胞 (AM)条件培养上清液与正常大鼠LFb共同培养 ,并给予不同浓度的Sim干预 ,利用3H 胸腺嘧啶核苷掺入法、3H 脯氨酸掺入法和Western杂交测定LFb增殖、胶原合成和Ras蛋白的翻译后修饰。结果 :Sim浓度依赖性的抑制肺纤维化 1周组AM条件培养上清液促LFb的增殖和胶原合成作用 (Sim 5 μM、10 μM、5 0 μM时 ,P <0 0 5 ) ,并抑制Ras蛋白加工。 结论 :辛伐他汀可以抑制肺纤维化阶段LFb增殖 ,减少胶原合成 ,可能通过影响Ras蛋白的加工起作用

Effect of simvastatin on rat lung fibroblasts in vitro

Objective:This study is to evaluate the effect of simvastatin (Sim) on proliferation and collagen synthesis of lung fibroblasts (LFb) incubated with alveolar macrophage (AM)|conditioned medium of bleomycin (BLM)|A5|induced rat pulmonary fibrosis.Method:Trypan blue exclusion, 3H|TdR incorporation and 3H|proline incorporation were assayed when LFb cultured in AM|conditioned medium on day 7 after bleomycin exposure.Western blot was carried out to determine the change of Ras process.Result:LFb proliferation and collagen synthesis were potently inhibited by Sim (5 μM,10 μM,50 μM vs. Sim 0 μM P <0 05) incubated with AM|conditioned medium in does|dependent manner with altering the post|translational modification of Ras.This effect can be blocked by the addition of mevalonate (100 μM).Conclusion:It is indicated that rat LFb proliferation and collagen synthesis with altering Ras process in fibrotic stage in vitro can be inhibited by Sim,necessitating further study of statins as the potential therapeutic medicines for pulmonary fibrosis. [