血管生成素-1在光气急性肺损伤中的作用

目的 观察大鼠光气染毒后Ang-1,NF-κB水平变化,探讨Ang-1在光气所致大鼠急性肺损伤中的作用机制.方法 (1)大鼠随机(随机数字法)分为光气组和空气组.(2)大鼠分为光气组、PDTC组和空气组.(3)大鼠气体和药物处理后常规饲养到预定时刻取肺汁算湿/干质量比值,BALF白细胞数、总蛋白和血清Ang-1水平.测动脉血气,检测肺组织Ang-1和NF-κB水平.结果 (1)光气染毒后48 h内血清Ang-1随着时间延长有降低趋势.(2)干预实验中,①光气组肺损伤指标与空气组比较均增高(P＜0.05);②光气组血清Ang-1、动脉血氧分压与空气组比较均降低(P＜0.05);③光气组肺损伤程度与干预组比较均增高(P＜0.05);④光气组血清Ang-1、动脉血氧分压与PDTC组比较均降低(P＜0.05).⑤肺蛋白印迹与免疫组化结果一致,结果显示:空气组Ang-1表达正常;光气组Ang-1表达明显减少;PDTC组与光气组相比Ang-1表达增高,与空气组相比表达减少.空气组NF-κB表达正常;光气组NF-κB表达明最增高;PDTC组与光气组相比NF-κB表达降低,与空气组相比表达增高.结论 (1)光气染毒后48 h内随着时间延长,血清Ang-1水平降低.(2) Ang-1通过NF-κB信号传导通路,减轻炎症因子介导的炎症反应,减轻肺脏内皮通透性,减轻急性肺脏损伤.

The study of the mechanism of the protective effect of angiogenin-1 on phosgene induced ALI in rats

Objective To observe the levels of Ang - 1 and NF-κB in lung tissue and to aseess the severity of ALI induced by phosgene in order to clarify the mechanism of the protective effect of Ang - 1 on phosgene induced ALI.Method Rats were randomly divided into phosgene group and air group.Another rats were randomly (random number) divided into phosgene group,phosgene + PDTC group and air group.Lung tissue was collected to weigh and calculate the wet / dry weight ratio,measure BALF,white blood cell count,total protein and Ang-1 at given time after exposure to phosgene/air and PDTC.The Ang - 1 and NF-κB levels in lung tissue were measured with Western blot and immunohistochemistry.Data were analyzed by using SPSS 16.0 statistical package and comparisons between groups were carried out byusing One-Way ANOVA analysis and LSD -t test,α ＜ 0.05.Results Serum angiopoietin -1 level became lesser within 48 hours after exposure to Phosgene.The severity of ALI became worser with time elapsing.Ccompare with air group,the severity of ALI in phosgene group was worser with time elapsing ( P ＜ 0.05).Compared with phosgene + PDTC group,the serum angiopoietin -1 and arterial oxygen partial pressure in phosgene group were lower ( P ＜ 0.05).The severity of ALI of rats in phosgene group were worser than that in phosgene + PDTC group ( P ＜ 0.05).Serum angiopoietin -1 and partial pressure of oxygen of rats in phosgene group were higher than those in phosgene + PDTC group ( P ＜ 0.05).Immunohistochemistry test showed that the expression of Ang-1 in lung tissue in air group were normal,and Ang-1 in phosgene group were significantly reduced,and Ang-1 in PDTC intervention group was higher than that in phosgene group and lower than that in air group.The above results were confirmed by Western blot test which was consistent with the results of immunohistochemistry test.Similarly,the levels of NF-κB in lung tissue determined by using both Western - blot and immunohistochemistry were consistant,and results of both methods showed that the expression of NF - κB in air group was normal,and it increased in phosgene group,and the expression of NF-κB in phosgene + PDTC group was lower than that in phosgene group.Conclusions The serum level of Ang-1 was decreasing within 48 hours after ALI.Ang-1 was negatively correlated with the sevfity of phosgene induced ALI.Ang-1 likely had an effect on NF-κB signaling pathway,ameliorating the inflammation mediated by cytokines,reducing lung endothelial permeability and in turn lessening the severity of ALI.