【摘要】 目的 探讨水通道蛋白(AQP)－1和AQP－5在失血性休克-内毒素二次打击所致大鼠肺损伤中的表达。方法 30只SD大鼠随机分为2组：假手术对照组（C组）、二次打击组（HS组），每组15只。建立“未控制性失血休克－内毒素” 二次打击大鼠模型，并按院前期90min、院内复苏期60min、院内观察期三期进行实验。实验结束前采血测动脉血气并比较二组大鼠存活率。测定肺泡灌洗液（BALF）蛋白（BALFpro）、肺通透指数（PPI）及肺组织湿/干重量比(W/D)；HE染色光镜下观察肺损伤程度；采用免疫组化分别测定肺组织AQP-1和 AQP-5的蛋白表达。 结果 与C组比较，HS组MAP、lac、PaO2、pH、BE、PPI、BALFpro、W/D等指标均明显恶化，肺组织损伤严重，大鼠存活率降低；与C组比较，HS组肺组织AQP-1和 AQP-5的表达显著降低(P <0.01)。结论 二次打击所致大鼠肺损伤时AQP-1和 AQP-5表达均明显降低，这可能是失血性休克后肺损伤肺水肿形成的重要原因之一。

【关键词】休克；失血性； 水通道蛋白－1；水通道蛋白－5
Decreased expression of aquaporin 1 and aquaporin 5 in uncontrolled hemorrhagic shock induced acute lung injury in a two-hit model in rats.
GAO Ju, ZHAO Wei-xian，XU Shao-qun, et al. Department of Anesthesiology, Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510120, China
【Abstract】 Objective To investigate the expression of aquaporin1and aquaporin5
in hemorrhagic shock induced acute lung injury in a two-hit model of hemorrhagic shock followed by mimicked infection. Methods Thirty SD rats were randomly assigned to the following two groups：control group(C group，surgery, no hemorrhage, and no resuscitation), two-hit model group (HS group). We used three-phased uncontrolled hemorrhagic shock model in rats. Hemorrhagic shock phase I began with blood withdrawal over 15 min, animals were subjected to massive hemorrhage [mean arterial pressure (MAP) = 35～ 40 mmHg for 60min and followed b免费论文网 【http://www.51lunwen.net】y intratracheal lipopolysaccharide 2 mg/kg (two-hit model). At hemorrhagic shock 90 min, resuscitation phase II of 60 min began with hemostasis, return of all the blood initially shed, plus fluids. Observation phase III was to 3.5h. After phase III, arterial blood gas and survival rates were recorded. Lung tissue was sampled to measure values of wet-to-dry lung weight ratio(W/D), pulmonary permeability index (PPI), BALF protein, and immunohistochemical used for detection of expression of AQP1and AQP5 . Results Compared with the control group, the HS group significantly decreased survival rates and increased pulmonary microvascular permeability and wet-to-dry lung weight ratio, and also decreased the AQP1and AQP5 expression in lung tissue. Conclusions These findings showed that the expression of AQP1 and AQP5 may play an important role in abnormal fluid transportation and formation of pulmonary edema in uncontrolled hemorrhagic shock –induced ALI.

【Key Words】Hemorrhage; Shock; Resuscitation; aquaporin

失血性休克并发急性肺损伤（ALI）的发生率高达40%[1]，其主要机制与肺内液体的渗出与清除失衡有关。水通道蛋白(Aquaporins, AQPs)是一组对水特异通透的膜蛋白分子，新近发现其与感染所致肺损伤、肺水肿及其严重程度密切相关[2]。但目前尚不明确失血性休克所致早期肺损伤是否与AQPs有关。因此，本研究通过建立“未控制性失血休克-内毒素” 二次打击大鼠模型，重点观察AQP1和AQP5在二次打击所致急性肺损伤时的表达变化，探讨此类急性肺损伤时肺水肿形成的机制。

材料与方法
动物分组和模型制作 健康成年清洁级SD大鼠30只（广州中医药大学实验动物中心提供），体重250～280g，动物实验前12h禁食、4h禁水，腹腔注射10％水合氯醛（0.3ml/kg）麻醉，将大鼠四肢及头部固定于恒温操作台上，颈部备皮后用碘伏消毒，分离右颈总动脉和静脉， 本文来自：免费论文网 [http://www.51lunwen.net]