ROCK抑制剂法舒地尔在高氧致新生大鼠肺纤维化中的作用.docVIP

ROCK抑制剂法舒地尔在高氧致新生大鼠肺纤维化中的作用 漆秀洁1，2，许峰1，2，方芳1，2 ，李静1，2 (400014 重庆，重庆医科大学附属儿童医院 PICU1 ,儿童发育疾病研究省部共建教育部重点实验室2) [摘要] 目的 探讨Rho激酶(Rho kinase,ROCK)抑制剂法舒地尔(fasudil,FAS)在高氧致新生SD大鼠肺纤维化中的作用。方法 新生SD大鼠24只按随机数字表法分为空气+NS组（正常对照组）、空气+FAS组、高氧+NS（生理盐水）组和高氧+FAS组,分别建立动物模型。在实验的第21d分别取各组新生大鼠行肺组织病理学检查；碱水解法测肺组织羟脯氨酸含量；免疫组化法和Western blot法检测肌成纤维细胞表型标志α-平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）的表达与分布。 结果 ①病理学检查示高氧+NS组肺组织结构紊乱，纤维化严重；高氧+FAS组较高氧+NS组明显改善。②肺组织羟脯氨酸测定结果显示，空气+NS组和空气+FAS组无明显差异（P＞0.05）；高氧+NS组与高氧+FAS组较空气+NS组明显增加（P＜0.05）；高氧+FAS组较高氧+NS明显降低（P＜0.05）。③α-SMA免疫组化和Western blot结果均显示，与空气+NS组相比，高氧+NS组和高氧+FAS组α-SMA的表达显著增强（P＜0.05），而高氧+FAS组较高氧+NS组明显减弱（P＜0.05）。 结论 ROCK抑制剂法舒地尔能一定程度改善高氧致新生大鼠肺纤维化，其机制可能是通过抑制肌成纤维细胞的产生从而减轻肺纤维化。 [关键词] 法舒地尔；α-平滑肌肌动蛋白；肌成纤维细胞；高氧；肺纤维化 Rock inhibitor fasudil in neonatal rats with hyperoxia-induced lung fibrosis Qi Xiujie1,2, Xu Feng1,2,Fang Fang1,2, Li Jing1,2 (Department of Pediatric Intensive Care Unit2 ,Children’s Hospital of Chongqing Medical University1，Chongqing 400014） No. [通讯作者] 李静，lijingwangyi@126.com [Abstract]: Objective:To investigate the Rho kinase inhibitor fasudil(FAS) in neonatal rats with hyperoxia-induced lung fibrosis.Method: According to the random number tables, twenty-four Sprague-Dawley neonatal rats were randomly divided into 4 groups: Air+NS(normal saline) group，Air+FAS group ,Hyperoxia+NS group and Hyperoxia+FAS group.After 21d, the subjects were sacrificed. The changes of lung histomorphology were observed; Hydroxyproline in the lung was detected by sample hydrolysis method; α-smooth muscle actin(α-SMA) protein expression in the lung was determined by immunohistochemistry method and Western-blot.Results: Pathological examination showed structural disorder and obvious fibrosis in lung tissue of Hyperoxia+NS group,and the sings of improvement in lung tissue of Hyperoxia+FAS group at 21d.The content of hydroxyproline and the α-SMA protein expression in lung tissue were both increased markedly at 21d of Hyperoxia+NS group and Hyperoxia+FAS group comp