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α7nAChR在盐酸戊乙奎醚减轻小鼠内毒素性急性肺损伤中的作用

Role ofα7nAChR in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury in mice
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摘要 目的评价α7烟碱型乙酰胆碱受体(α7nAChR)在盐酸戊乙奎醚减轻小鼠内毒素性急性肺损伤中的作用。方法SPF级健康雄性C57BL/6小鼠40只,6~8周龄,体质量18~25 g,采用随机数字表法分为4组(n=10):对照组(C组)、急性肺损伤组(ALI组)、盐酸戊乙奎醚组(PHC组)和α7nAChR抑制剂MLA组(MLA组)。采用腹腔注射脂多糖15 mg/kg的方法制备小鼠内毒素性急性肺损伤模型。PHC组于模型制备前30 min腹腔注射盐酸戊乙奎醚2 mg/kg,MLA组于给予盐酸戊乙奎醚前10 min腹腔注射MLA 10 mg/kg,C组腹腔注射等量生理盐水。与注射内毒素后6 h时处死小鼠取肺组织,HE染色法观察病理学结果,确定肺组织湿重/干重(W/D)比值,ELISA法检测TNF-α、IL-1β和IL-10含量,Western blot法检测α7nAChR表达。结果与C组比较,ALI组、PHC组和MLA组肺组织W/D比值、TNF-α和IL-1β含量升高,IL-10含量降低,α7nAChR表达上调(P<0.05);与ALI组比较,PHC组肺组织W/D比值、TNF-α和IL-1β含量降低,IL-10含量升高,α7nAChR表达上调(P<0.05);与PHC组比较,MLA组肺组织W/D比值、TNF-α和IL-1β含量升高,IL-10含量降低,α7nAChR表达下调(P<0.05)。PHC组肺组织病理学损伤较ALI组减轻,盐酸戊乙奎醚的这种作用则被α7nAChR抑制剂MLA部分逆转。结论α7nAChR参与了盐酸戊乙奎醚减轻小鼠内毒素性急性肺损伤的过程。 Objective To evaluate the role ofα7 nicotinic acetylcholine receptor(α7nAChR)in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury(ALI)in mice.Methods Forty SPF healthy male C57BL/6 mice,aged 6-8 weeks,weighing 18-25 g,were divided into 4 groups(n=10 each)using a random number table method:control group(group C),ALI group,penehyclidine hydrochloride group(PHC group),andα7nAChR inhibitor MLA group(MLA group).ALI was induced by intraperitoneal injection of lipopolysaccharide 15 mg/kg in anesthetized animals,while normal saline was given instead in group C.In PHC group,penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected at 30 min before developing the model.MLA 10 mg/kg was intraperitoneally injected at 10 min before administration of penehyclidine hydrochloride in MLA group.Mice were sacrificed at 6 h after lipopolysaccharide administration,and lung tissues were collected for microscopic examination of the pathological changes(by HE staining)and for determination of the wet/dry weight ratio(W/D ratio),content of tumor necrosis factor-alpha(TNF-α),interleukin-1beta(IL-1β)and IL-10(by enzyme-linked immunosorbent assay)and expression ofα7nAChR(by Western blot).Results Compared with C group,the W/D ratio and contents of TNF-αand IL-1βwere significantly increased,the content of IL-10 was decreased,and the expression ofα7nAChR was up-regulated in ALI,PHC and MLA groups(P<0.05).Compared with ALI group,the W/D ratio and contents of TNF-αand IL-1βwere significantly decreased,the content of IL-10 was increased,and the expression ofα7nAChR was up-regulated in PHC group(P<0.05).Compared with PHC group,the W/D ratio and contents of TNF-αand IL-1βwere significantly increased,the content of IL-10 was decreased,and the expression ofα7nAChR was down-regulated in MLA group(P<0.05).Compared with ALI group,the pathological changes of lung tissues were significantly mitigated in PHC group,while this effect of PHC was partially reversed byα7nAChR inhibitor MLA.Conclusionsα7nAChR is involved in penehyclidine hydrochloride-induced reduction of endotoxin-induced ALI in mice.
作者 张晓艳 赵军博 周尚尤 魏晓永 王涛 王玉霞 姜丽华 Zhang Xiaoyan;Zhao Junbo;Zhou Shangyou;Wei Xiaoyong;Wang Tao;Wang Yuxia;Jiang Lihua(Department of Anesthesiology,The Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2023年第4期481-484,共4页 Chinese Journal of Anesthesiology
关键词 Α7烟碱型乙酰胆碱受体 胆碱能拮抗剂 内毒素类 急性肺损伤 alpha7 nicotinic acetylcholine receptor Cholinergic antagonists Endotoxins Acute lung injury
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