氢吗啡酮对急性肺损伤大鼠水通道蛋白1、5表达的影响  

Effect of hydromorphone on the expression of aquaporin-1 and aquaporin-5 during acute lung injury in rats

作　　者：李心怡[1] 王庆元 张静[1] 王锦[1] 王成夭[1] LI Xinyi;WANG Qingyun;ZHANG Jing;WANG Jin;WANG Chengyao(Dept.of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China;Dept.of Anesthesiology,The People’s Hospital of Tuanfeng,Huanggang 438800,Hubei,China)

机构地区：[1]武汉大学中南医院麻醉科,湖北武汉430071 [2]团风县人民医院麻醉科,湖北黄冈438800

出　　处：《武汉大学学报（医学版）》2022年第5期716-720,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:82002033);湖北省自然科学基金资助项目(编号:2020CFB199)。

摘　　要：目的:研究氢吗啡酮对内毒素性急性肺损伤(ALI)大鼠水通道蛋白(AQP)-1和AQP-5表达的影响。方法:健康雄性SD大鼠36只,体质量300~350 g,随机分为3组(n=12):假手术组(Sham组)、急性肺损伤组(ALI组)和氢吗啡酮预先给药组(HYD组)。ALI组和HYD组采用静脉注射LPS 8 mg/kg建立ALI模型。HYD组于注射LPS前10 min静脉注射氢吗啡酮0.1 mg/kg。LPS注射后6 h处死大鼠,取肺组织,测定肺湿/干重(W/D)比值及肺通透指数(LPI),HE染色观察肺组织病理学改变,ELISA法测定肺组织TNF-α、IL-1β含量,RT-PCR法和Western Blot法测定AQP-1、AQP-5 mRNA及蛋白表达。结果:与Sham组比较,ALI组和HYD组肺组织W/D比值、LPI及病理学损伤评分增高,TNF-α、IL-1β含量升高,AQP-1、AQP-5 mRNA及蛋白表达下调(P<0.05),W/D比值及病理学损伤评分均增高(P<0.05);与ALI组比较,HYD组肺组织W/D比值、LPI及病理学损伤评分降低,TNF-α、IL-1β含量降低,AQP-1、AQP-5 mRNA及蛋白表达上调。结论:氢吗啡酮可减轻内毒素症大鼠急性肺损伤,可能与抑制炎症反应和上调AQP-1、AQP-5的表达有关。Objective: To evaluate the effects of hydromorphone(HYD) preconditioning on the expression of aquaporin(AQP)-1 and AQP-5 during acute lung injury(ALI) induced by lipopolysaecharide(LPS)in rats. Methods: A total of 36 male Sprague-Dawley rats(300-350 g)were randomly divided into 3groups(n=12 in each group) randomly as sham group(Group Sham), ALI group(Group ALI), and hydromorphone group(Group HYD). ALI models were developed by intravenous injection of LPS 8mg/kg in Group ALI and Group HYD, while equal volume of normal saline was given in Group Sham. Hydromorphone 0. 1 mg/kg was injected intravenously in Group HYD 10 min before LPS injection, while the equal volume of normal saline was injected in Group ALI and Group Sham. Rats were sacrificed at the end of 6 h after LPS injection, and pulmonary specimens were obtained for pathological observation(lung injury score) and determination of wet/dry lung weight(W/D) ratio and lung permeability index(LPI), concentrations of TNF-α and IL-1β were assayed by ELISA, and then the expression of AQP-1 and AQP-5 at mRNA(RT-PCR) and protein(Immunohistochemistry and Western Blot) levels were determined. Results: Compared with that respectively in Group Sham,lung injury score, W/D ratio, LPI, and concentrations of TNF-α and IL-1β were significantly increased, and the expression of AQP-1 and AQP-5 mRNA levels were decreased in groups ALI and HYD(P<0. 05). Compared with that respectively in Group ALI, lung injury score, W/D ratio,LPI, and concentrations of TNF-α and IL-1β were significantly decreased, and the expression of AQP-1 and AQP-5 mRNA levels were increased in Group HYD(P<0. 05). Conclusion: Hydromorphone may attenuate ALI and reduce inflammatory response via down-regulation of AQP-1 and AQP-5.

关 键 词：氢吗啡酮 急性肺损伤 炎症反应 水通道蛋白 

分 类 号：R614.2[医药卫生—麻醉学]