1,25-二羟维生素D_3抑制RhoA/ROCK通路减轻幼鼠海水淹溺型肺损伤的实验研究  

1,25-( OH)2Vit D3alleviates seawater drowning-induced acute lung injury in young rats by inhibiting Rho A / ROCK pathway

作　　者：罗建峰[1] 吴华杰[1] 石曌玲[1] 张敏龙[2] 金发光[2] 

机构地区：[1]第四军医大学西京医院儿科,西安710032 [2]第四军医大学唐都医院呼吸与危重症医学科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2015年第5期25-28,共4页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金(81270124)

摘　　要：目的探讨1,25-二羟维生素D3对幼鼠海水吸入型肺损伤的干预作用及其机制。方法32只SD幼鼠随机分为空白对照组、海水处理组、活性Vit D3处理组和地塞米松处理组,每组8只。海水处理组幼鼠给予气管内灌注3 ml/kg海水,Vit D3处理组和地塞米松处理组在海水处理组的基础上分别给予25μg/kg Vit D3和10 mg/kg地塞米松灌胃处理。分别检测各组肺组织湿干比和通透性变化,ELISA法检测肺组织中炎症因子肿瘤坏死因子-α(TNF-α)和白细胞-1β(IL-1β)的表达,Western blot检测GTPRho A和磷酸化MYPT-1的表达变化。结果与正常对照组比较,海水气管内滴入4 h后幼鼠肺部组织出现明显炎症和水肿,炎症因子TNF-α和IL-1β的表达显著增高,Rho A的活化和MYPT-1磷酸化增加;1,25-二羟维生素D3和地塞米松干预可显著减轻海水导致的肺组织损伤,减少了TNF-α和IL-1β的释放,并且抑制了Rho A的活化和MYPT-1的磷酸化。结论 Rho A/ROCK通路参与幼鼠海水吸入型肺损伤的发展,1,25-二羟维生素D3能够通过调节该信号通路减轻肺损伤。Objective To observe the therapeutic effect of 1,25-（ OH）2Vit D3 in seawater aspirationinduced acute lung injury of young rats and explore the possible mechanisms. Methods Young SD rats were randomly divided into 4 groups,8 in each group： control group,seawater group,Vit D3pre-treated group and dexamethasone pre-treated group. Seawater（ 3 ml / kg） was instilled into the airway of young rats in seawater group. Rats in Vit D3 group and dexamethasone group were injected with 25 μg / kg Vit D3 or 10 mg / kg dexamethasone followed by seawater. W / D ratio and lung tissue permeability detection was carried out after modeling. The expression of TNF-α and IL-1β were measured by ELISA and the expression of GTP-Rho A and phospho-MYPT1 were measured by Western blot. Results Compared with control group, lung tissue inflammation and edema were obvious and the expression of TNF-α and IL-1β were increased after 4 h seawater stimulation. The expression of GTP-Rho A and phospho-MYPT1 were up-regulated. However,administration of1,25-（ OH）2Vit D3 attenuated lung inflammation and edema,suppressed the release of TNF-α and IL-1β,and inhibited the expression of GTP-Rho A and phospho-MYPT1. Conclusion Rho A / ROCK pathway plays important role in the seawater aspiration-induced acute lung injury of young rats and 1,25-（ OH）2Vit D3 attenuated lung injury by inhibiting Rho A / ROCK pathway.

关 键 词：急性肺损伤 海水 1 25-二羟维生素D3 RHO A/ROCK 幼鼠 

分 类 号：R563[医药卫生—呼吸系统]