右美托咪啶减轻急性肺损伤的机制研究  

Mechanism of dexmedetomidine in alleviating acute lung injury

作　　者：李洁[1] 何凤娟 范国华[1] LI Jie;HE Feng-juan;FAN Guo-hua(Department of Thoracic Surgery,People’s Hospital of Wuhan University,Wuhan Hubei 430061,China;Department of Breast and Thyroid Surgery,People’s Hospital of Wuhan University,Wuhan Hubei 430061,China)

机构地区：[1]武汉大学人民医院胸外科,湖北武汉430061 [2]武汉大学人民医院乳甲外科,湖北武汉430061

出　　处：《局解手术学杂志》2021年第10期852-856,共5页Journal of Regional Anatomy and Operative Surgery

基　　金：湖北省自然科学基金(2020cfb609)。

摘　　要：目的探讨右美托咪啶(Dex)对小鼠急性肺损伤(ALI)的影响及潜在作用机制。方法将32只C57BL/6雄性小鼠随机分为空白对照组(Sham组)、右美托咪啶组(Dex组)、脂多糖组(LPS组)和药物干预组(LPS+Dex组)。LPS组和LPS+Dex组小鼠通过腹腔注射LPS(10 mg/kg)构建小鼠ALI模型,Dex组及LPS+Dex组小鼠腹腔注射Dex(40μg/kg),Sham组和LPS组注射等剂量生理盐水。LPS注射12 h后,采用HE染色比较各组小鼠肺损伤状况;qRT-PCR检测各组小鼠肺组织中促炎性细胞因子IL-1β、TNF-α、IL-6和MCP-1 mRNA的表达;Western blot检测各组小鼠肺组织中GPX4、COX2和转录因子红系2相关因子2(Nrf2)蛋白的表达。结果与Sham组相比,LPS组小鼠肺损伤评分明显升高(P<0.05),促炎性细胞因子IL-1β、TNF-α、IL-6和MCP-1 mRNA表达水平均明显升高(P<0.05),肺组织铁死亡标志物GPX4蛋白表达水平明显降低(P<0.05),COX2蛋白表达水平则明显升高(P<0.05),肺组织中Nrf2蛋白表达水平明显降低(P<0.05)。与LPS组相比,LPS+Dex组小鼠肺损伤评分明显降低(P<0.05),IL-1β、TNF-α、IL-6和MCP-1 mRNA表达水平明显降低(P<0.05),GPX4的蛋白表达水平明显升高(P<0.05),COX2蛋白表达水平则明显降低(P<0.05),Nrf2的蛋白表达水平也明显升高(P<0.05)。结论Dex可能通过激活Nrf2抑制小鼠肺组织铁死亡,进而发挥肺保护作用。Objective To investigate the effect of dexmedetomidine(Dex)on acute lung injury(ALI)in mice and its potential mechanism.Methods A total of 32 C57BL/6 male mice were randomly divided into the blank control group(Sham group),the dexmedetomidine group(Dex group),the lipopolysaccharides(LPS group)and the drug intervention group(LPS+Dex group).The mice of the LPS group and the LPS+Dex group were injected intraperitoneally with LPS(10 mg/kg)to establish the mouse ALI model.The mice of the Dex group and the LPS+Dex group were injected intraperitoneally with Dex(40μg/kg),and the Sham group and the LPS group were injected with equal doses of normal saline.After 12 hours of LPS injection,HE staining was used to compare the lung injury status of mice in each group;qRT-PCR was used to detect the mRNA expression of pro-inflammatory cytokines including IL-1β,TNF-α,IL-6 and MCP-1 in the lung tissue of mice in each group;Western blot was used to detect the protein expression of GPX4,COX2 and nuclear factor-erythroid 2-related factor 2(Nrf2)in the lung tissue of mice in each group.Results Compared with the Sham group,the lung injury score of mice in the LPS group was significantly increased(P<0.05),the mRNA expression levels of the pro-inflammatory cytokines including IL-1β,TNF-α,IL-6 and MCP-1 were significantly increased(P<0.05),the protein expression level of ferroptosis marker GPX4 in the lung tissue was significantly decreased(P<0.05),while the protein expression level of COX2 was significantly increased(P<0.05),and the protein expression level of Nrf2 in the lung tissue was significantly decreased(P<0.05).Compared with the LPS group,the lung injury score of mice in the LPS+Dex group was significantly dereased(P<0.05),the mRNA expression levels of IL-1β,TNF-α,IL-6 and MCP-1 were significantly decreased(P<0.05),the protein expression level of GPX4 was significantly increased(P<0.05),while the protein expression level of COX2 was significantly decreased(P<0.05),and the protein expression level of Nrf2 was also significa

关 键 词：右美托咪啶 急性肺损伤 NRF2 铁死亡 

分 类 号：R614[医药卫生—麻醉学]