地塞米松和法舒地尔对油酸致小鼠急性肺损伤伤情的影响  

Both dexamethasone and fasudil attenuate oleic acid-induced acute lung injury in mice

作　　者：陈星云[1] 杨楠[1] 赵艳[1] 熊仁平[1] 李平[1] 刘苹[1] 钟小龙[1] 周元国[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所分子生物学中心,重庆400042

出　　处：《第三军医大学学报》2009年第10期952-954,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金(30470988);教育部创新团队基金(IRT0712)~~

摘　　要：目的探讨地塞米松和法舒地尔(fasudil)对油酸致小鼠急性肺损伤的影响及ROCK(Rho-associated coiledcoil forming kinase)在其中的作用。方法采用油酸致C57小鼠急性肺损伤模型,观察伤后24h各组肺组织病理及肺含水率、ROCK活性、ROCK1和ROCK2蛋白含量及IL-1βmRNA的变化。结果地塞米松和法舒地尔均可显著减轻油酸肺组织中炎性细胞浸润、肺出血等病理变化,降低肺含水率(P<0.05),抑制肺组织ROCK活性(P<0.05),降低IL-1βmRNA的表达水平;地塞米松对ROCK1的表达水平无影响,但可增强ROCK2的表达,法舒地尔对ROCK1和ROCK2的表达水平均无影响。结论地塞米松和法舒地尔均可通过抑制肺组织内炎性细胞浸润明显减轻油酸引起的急性肺损伤,而地塞米松的治疗作用可能与对其ROCK活性的抑制有关。Objective To investigate the effects of dexamethasone and fasudil on oleic acid-induced acute lung injury in mice and the roles of Rho-associated coiled-coil forming kinase （ROCK） in this process. Methods Totally 140 SPF grade C57 mice were randomly and equally divided into 4 groups： normal control, acute lung injury group, dexamethasone group and fasudil group. The animals of the later 3 groups were inflicted by an injection of 0.6 mg/g oleie acid through tail vein to induce acute lung injury model, and then followed by injecting normal saline at same volume, 5 mg/kg dexamethasone and 10 mg/kg fasudil respectively. The normal control group only received normal saline injection. All mice were sacrificed 24 h after injury and the lungs were resected. The pulmonary pathology was examined by HE staining, the activities of ROCK1 and ROCK2 were assayed by ELISA, the expression levels of ROCK1 and ROCK1 protein were detected by Western blot analysis, and the expression level of IL-β mRNA were observed by real-time PCR. Results After treatment with dexamethasone or fasudil, the bleeding and infiltration in lung tissue induced by oleic acid were attenuated, the lung water content was decreased significantly, the activities of ROCK1 and ROCK2 were inhibited, and the expression level of IL-1β mRNA was declined. Dexamethasone had no effect on the expression level of ROCKI but upregulated the expression of ROCK2 significantly. Both of the expression level of ROCK1 and ROCK2 had no significant changes after treatment with fasudil. Conclusion Both of dexamethasone and fasudil attenuate the lung injury induced by oleic acid through inhibiting the activity of ROCK. The different effects of dexamethasone and fasudil on the expression levels of ROCKI and ROCK2 suggest that effects of ROCK1 and ROCK2 in the treatment of dexamethasone or fasudil in oleic acid induced lung injury are different.

关 键 词：急性肺损伤 地塞米松 法舒地尔 ROCK1 ROCK2 

分 类 号：R563.05[医药卫生—呼吸系统] R969[医药卫生—内科学]