盐酸戊乙奎醚减轻大鼠内毒素性肺损伤的机制:与Toll样受体4的关系  

Mechanism of penehyclidine hydrochloride alleviating endotoxin-induced lung injury in rats:relationship with Toll-like receptor 4

作　　者：魏晓永[1] 王涛[1] 赵军博[1] 顾士敏[1] 刘博[1] 王丽娟[1] 姜丽华[1] 魏磊[2] Wei Xiaoyong;Wang Tao;Zhao Junbo;Gu Shimin;Liu Bo;Wang Lijuan;Jiang Lihua;Wei Lei(Department of Anesthesiology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Anesthesiology,Suzhou Municipal Hospital,Suzhou Hospital Affiliated to Nanjing Medical University,Suzhou 215002,China)

机构地区：[1]郑州大学第三附属医院麻醉科,郑州450052 [2]南京医科大学附属苏州医院麻醉科,苏州215002

出　　处：《中华麻醉学杂志》2022年第9期1108-1111,共4页Chinese Journal of Anesthesiology

基　　金：河南省医学科技攻关计划项目(LHGJ20190387)。

摘　　要：目的评价肺组织Toll样受体4(TLR4)在盐酸戊乙奎醚减轻大鼠内毒素性肺损伤机制中的作用。方法清洁级健康雄性SD大鼠24只,10周龄,体重220~250 g,采用随机数字表法分为4组(n=6):生理盐水组(NS组)、内毒素性肺损伤组(ALI组)、盐酸戊乙奎醚+生理盐水组(PHC+NS组)和盐酸戊乙奎醚+内毒素性肺损伤组(PHC+ALI组)。采用气道内滴注LPS 5 mg/kg的方法制备大鼠内毒素性肺损伤模型;PHC+ALI组气道内滴注LPS后即刻腹腔注射盐酸戊乙奎醚2 mg/kg,NS组气道内滴注相应容量生理盐水,PHC+NS组气道内滴注生理盐水后即刻腹腔注射盐酸戊乙奎醚2 mg/kg。气道内滴注LPS后6 h麻醉下处死大鼠,进行肺灌洗,采用ELISA法检测肺泡灌洗液TNF-α和IL-1β的浓度;取肺组织标本,计算肺湿干重比值(W/D比值),光镜下观察病理学结果,采用免疫组化法检测TLR4表达,采用RT-PCR法检测TLR4 mRNA表达。结果与NS组和PHC+NS组相比,ALI组W/D比值、肺泡灌洗液TNF-α和IL-1β浓度升高,肺组织TLR4及其mRNA表达上调(P<0.01),肺组织病理学损伤加重;与ALI组相比,PHC+ALI组W/D比值、肺泡灌洗液TNF-α和IL-1β浓度降低,肺组织TLR4及其mRNA表达下调(P<0.01),肺组织病理学损伤减轻。结论盐酸戊乙奎醚减轻大鼠内毒素性肺损伤的机制可能与降低TLR4活性而抑制炎症反应有关。Objective To evaluate the role of Toll-like receptor 4(TLR4)in the mechanism by penehyclidine hydrochloride alleviating lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 10 weeks,weighing 220-250 g,were divided into 4 groups(n=6 each)according to the random number table method:normal saline group(NS group),endotoxin-induced ALI group(ALI group),penehyclidine hydrochloride+normal saline group(PHC+NS group)and penehyclidine hydrochloride+endotoxin-induced ALI group(PHC+ALI group).ALI was induced by intratracheal instillation of LPS 5 mg/kg in anesthetized animals.In group PHC+ALI,penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of LPS.The equal volume of normal saline was injected into the airway in group NS,and penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of normal saline in group PHC+NS.The rats were sacrificed at 6 h after intratracheal instillation of LPS or normal saline,and lungs were removed.The lung was lavaged and broncho-alveolar lavage fluid(BALF)was collected for determination of concentrations of tumor necrosis factor-alpha(TNF-α)and interleukin-1beta(IL-1β)by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathological changes(with a light microscope)and for determination of wet to dry lung weight ratio(W/D ratio)and TLR4 protein and mRNA expression(by immuno-histochemistry or real-time polymerase chain reaction).Results Compared with group NS and group PHC+NS,the W/D ratio and concentrations of TNF-αand IL-1βin BALF were significantly increased,the expression of TLR4 protein and mRNA in lung tissues was up-regulated(P<0.01),and the pathological changes of lung tissues were aggravated in group ALI.Compared with group ALI,the W/D ratio and concentrations of TNF-αand IL-1βin BALF were significantly decreased,the expression of TLR4 protein and mRNA in lun

关 键 词：胆碱能拮抗剂 内毒素类 急性肺损伤 TOLL样受体4 

分 类 号：R614[医药卫生—麻醉学]