ROCK抑制剂法舒地尔在高氧致新生大鼠肺纤维化中的作用

Rho kinase inhibitor fasudil in neonatal rats with hyperoxia-induced lung fibrosis

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+生理盐水(NS)组(正常对照组)、空气+FAS组、高氧+NS组和高氧+FAS组,分别建立动物模型。在实验的第21天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病理学检查结果显示,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检测结果均显示,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。

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 ＋ normal saline （NS） group, air ＋ FAS group, hyperoxia ＋ NS group and hyperoxia ＋ FAS group. After 21 d, the subjects were sacrificed. The changes of lung histomorphology were observed. Hydroxyproline in the lung was detected by sample hydrolysis method. a-smooth muscle aetin （α-SMA） protein expression in the lung was determined by immunohistochemistry assay and Western blotting. Results Pathological examination showed structural disorder and obvious fibrosis in the lung tissues of hyperoxia ＋ NS group and the signs of improvement in the lung tissues of hyperoxia ＋ FAS group at 21 d. The content of hydroxyproline and α-SMA protein expression in lung tissues were both increased markedly at 21 d in the hyperoxia ＋ NS group and hyperoxia ＋ FAS group compared with the air groups, and were significantly lower at 21 d in the hyperoxia ＋ FAS group than in the hyperoxia ＋ NS group. Conclusion Rho kinase inhibitor fasudil has obvious therapeutic effects on hyperoxia-induced lung fibrosis, probably through myofibroblast inhibition.