一氧化碳饱和血红蛋白通过抑制TREM-1/TLR4通路发挥对高原低氧心脏损伤的保护作用  

CO-HBOC played protective role on high-altitude hypoxia-induced cardiac injuries by suppressing TREM-1/TLR4 pathway

作　　者：刘汉林 李茸源 肖奕君 易小波 吴畏(指导) LIU Hanlin;LI Rongyuan;XIAO Yijun;YI Xiaobo;WU Wei(Department of Anesthesiology,the General Hospital of Western Theater Command,Chengdu 610083,China)

机构地区：[1]西南医科大学临床医学院,泸州646000 [2]成都医学院,成都610500 [3]西部战区总医院麻醉科,成都610083

出　　处：《中国免疫学杂志》2023年第4期682-686,共5页Chinese Journal of Immunology

基　　金：四川省科学技术厅项目(2018RZ0135)。

摘　　要：目的:探究一氧化碳饱和血红蛋白(CO-HBOC)能否通过抑制TREM-1/TLR4通路调节免疫,减轻炎症反应,发挥对高原低氧心脏损伤的保护作用。方法:30只雄性C57/BL6小鼠随机分为常氧生理盐水(NS)组、高原低氧生理盐水(HS)组和高原低氧CO-HBOC(HC)组。低氧组置于低压低氧动物实验舱模拟海拔5 500 m高原环境。实验舱运行时间为24 h/d,控制昼夜比约12 h∶12 h,连续低氧处理7 d;NS组置于相同条件的常压常氧环境下饲养。在建模过程中,HC组给予0.3 g Hb/kg/d CO-HBOC连续处理3 d,NS组和HS组给予等量生理盐水。采用心肌酶和心肌组织HE染色分析评估心肌组织损伤程度,qPCR和ELISA分别检测心肌组织和血浆中IL-1β、TNF-α表达,Western blot检测心肌组织髓源细胞表面触发受体1(TREM-1)、Toll样受体4(TLR4)表达。结果:(1)HS组小鼠CK-MB、LDH较NS组明显升高,但CO-HBOC处理后小鼠心肌损伤减轻;(2)HE染色显示HS组小鼠较NS组出现明显心肌细胞水肿、核坏死、灶状变性并伴有炎症细胞浸润,而HC组小鼠心肌水肿减轻,炎症细胞减少;(3)HS组小鼠心肌组织和血浆中IL-1β、TNF-α较NS组明显升高,HC组中IL-1β、TNF-α较HS组明显降低;(4)HS组小鼠心肌组织中TREM-1、TLR4较NS组增高,而HC组小鼠中二者表达量较HS组显著减少。结论:CO-HBOC可通过调节免疫、抑制炎症,发挥对高原低氧心肌的保护作用,其保护作用可能与抑制TREM-1/TLR4通路有关。Objective:To investigate whether carbon monoxide-saturated hemoglobin-based oxygen carriers(CO-HBOC)played protective role on high-altitude hypoxia-induced cardiac injury by suppressig TREM-1/TLR4 pathway to regulate immunity and then alleviate inflammation.Methods:Total 30 male C57/BL6 mice were randomly divided into normoxia+saline(NS)group,hypobaric hypoxia+saline(HS)group and hypobaric hypoxia+CO-HBOC(HC)group.Mice of hypobaric hypoxia were placed in a large chamber,which can mimic 5500 m high-altitude environment.The chamber was operated 24 h/d,and the circulation was controlled approxi‐mately to be 12 h∶12 h,mice were kept in low oxygen treatment continuously for 7 d.NS group was fed under normobaric normoxia condi‐tion.During hypoxia period,HC group was injected Hb 0.3 g Hb/kg/d CO-HBOC successively for three days,NS group and HS group were given equal volume saline.Cardiac enzymes and myocardial pathological changes which analyzed by HE staining were used to evaluate degree of cardial injury.IL-1βand TNF-αin cardiac tissue and plasma were examined by qPCR and ELISA.Triggering receptor expressed on myeloid cells-1(TREM-1)and Toll-like receptor 4(TLR4)in cardiac were assayed by Western blot.Results:①CK-MB,LDH in HS group were increased compared with NS group,while treatment of CO-HBOC were mitigated cardial injury;②Patho‐logical changes including myocardial edema,nuclear necrosis,focal degeneration and inflammatory cell infiltration were obvious in HS group,yet cardial edema and iflammatory infiltration were relieved in HC group;③IL-1βand TNF-αin cardiac tissue and plasma of HS group were rised apparently,while both of them were decreased in HC group;④Expressions of TREM-1 and TLR4 in HS group were increased compared with NS group,while both of them in HC group were significantly reduced conpared with HS group.Conclu⁃sion:Protection of CO-HBOC on high-altitude myocadium has been achevied by ajusting immunity and inhibiting inflammation,and its protective role may involve suppression of

关 键 词：高原低氧 心肌 一氧化碳饱和血红蛋白 髓源细胞表面触发受体1 免疫 炎症 

分 类 号：R392.9[医药卫生—免疫学]