高原失血性休克大鼠相关急性肺损伤病变及发病机制  

Evolution and mechanism of acute lung injury following hemorrhagic shock in a rodent model at plateau

作　　者：高晓华[1] 曹虹[2] 耿智隆[2] 

机构地区：[1]福建医科大学附属第二医院麻醉科,福建省泉州市362000 [2]兰州军区兰州总医院麻醉手术科

出　　处：《临床麻醉学杂志》2017年第5期492-496,共5页Journal of Clinical Anesthesiology

基　　金：全军面上基金课题(CLZ14L001);兰州军区面上基金课题(CLZ12JB11)

摘　　要：目的探讨高原失血性休克相关急性肺损伤(acute lung injury,ALI)病变及发病机制。方法雄性Wistar大鼠72只,体重280~320g,随机分为六组:假手术组(Sham组)、休克15min组(HS15组)、休克30min组(HS30组)、休克45min组(HS45组)、休克60min组(HS60组)和休克90min组(HS90组),每组12只。建立高原大鼠失血性休克模型后,Sham组麻醉置管后不予失血,仅观察90min即刻处死,其余五组分别按照15、30、45、60和90min观察终止时间窗维持于休克状态。光镜下观察肺组织病理变化,测定肺湿/干重比(W/D)、计算肺通透指数,同时测定肺组织髓过氧化物酶(MPO)、总超氧化物歧化酶(T-SOD)的活性和丙二醛(MDA)的浓度,采用ELISA法检测肺组织中TNF-α和IL-10的浓度。采用免疫组化法检测肺组织中claudin-3和claudin-4的表达和分布。结果与Sham组比较,休克造成不同程度的肺损伤,且与休克维持时间成正比。在休克15~30min,大鼠肺组织W/D、肺通透指数、MPO、MDA、TNF-α、T-SOD和IL-10的变化甚微,在此之后,随着时间的延长,肺W/D、肺通透指数、MPO活性、MDA浓度和TNF-α浓度明显升高,同时伴随SOD活性和IL-10浓度的明显下降(P<0.05)。claudin-3和claudin-4在肺上皮细胞和内皮细胞处的表达明显错位并减少(P<0.05)。结论高原环境下,遭受失血性休克的大鼠血流动力学在短时间代偿后,病变呈现螺旋式恶化。且随着休克的延续,大鼠体内炎性/抗炎、氧化/抗氧化稳态失衡,导致肺上皮细胞内claudin-3和claudin-4流失,呈现出急性肺损伤的表现。Objective To explore the pathogenesis of acute lung injury in rats suffering hemor- rhagic shock at plateau. Methods Seventy-two male Wistar rats, weighing 280-320 g, were random- ized into 6 groups （n= 12）. sham group （group Sham）, hemorrhagic shock for 15 rain （group HS15）, hemorrhagic shock for 30 rain group （group HS30）, hemorrhagic shock for 45 min group （group H845）, hemorrhagic shock for 60 rain group （group HS60） and 90 min group （group HS90）. Hemorrhagic shock model of Wistar rats was reproduced at plateau. The rats were only anesthetized, no shock and were sacrificed after 90 rain in group Sham. The other groups were different in bleeding time and then were respectively sacrificed at 15, 30, 45, 60 and 90 min after shock. The pathological changes in the lungs were observed with light microscope. Wet to dry weight ratio （W/D）, lung per- meability index （LPI）, myeloperoxidase （MPO） activity, malondialdehyde （MDA） and superoxide dismutase （SOD） in lung were measured. Enzyme-linked immunosorbent assay was used to detect the TNF-a and IL-10 in lung tissue, the expression and distribution of claudin-3 and claudin-4 in lung tis- sue was verified by immunohistochemistry method. Results Compared with group Sham, shock causes acute lung injury at different degree, and was positively correlated with the duration of shock, during the pe- riod of 15 to 30 rain, it merely rendered a slight change in lung W/D, LPI, MPO, MDA, TNF-a, T-SOD and IL-10. Subsequently, along with time prolonged, lung W/D, neutrophils in BALF, LPI, MPO, MDA, TNF-a were significantly elevated, while T-SOD and IL-10 were notably reduced （P〈0. 05）. Immunohis- tochernical results showed that claudin-3 and daudin-4 expression in lung epithelial cells and endothelial cells expressed at low levels and dislocated （P〈0.05）. Conclusion After a short time compensatory lesions, the change of rats＇ hemodynamic stability suffering severe hemorrhagic shock showed a spiral down- ward. Along with t

关 键 词：失血性休克 高原 急性肺损伤 炎性反应 氧化应激 

分 类 号：R459.7[医药卫生—急诊医学]