首页|TREM2缺失加重小鼠肺缺血再灌注损伤的机制研究

TREM2缺失加重小鼠肺缺血再灌注损伤的机制研究

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目的:探讨2型髓系细胞触发受体(TREM2)对肺缺血再灌注损伤(LIRI)的影响及其可能的调控机制.方法:将C57BL/6J雄性小鼠(WT)及TREM2敲除鼠(TREM2 KO)各12只,随机分成WT小鼠假手术组(WT组)、TREM2 KO小鼠假手术组(TREM2 KO组)、WT小鼠LIRI组(WT+LIRI组)、TREM2 KO小鼠LIRI组(TREM2 KO+LIRI组),每组6只.WT+LIRI组和TREM2 KO+LIRI组采用夹闭左肺肺门1h,再灌注24h的方法制备小鼠LIRI模型,WT组和TREM2 KO组仅开胸不夹闭肺门;通过蛋白免疫印迹(western blotting)、免疫荧光、实时荧光定量PCR(RT-qPCR)、苏木精—伊红(HE)染色、测定肺湿干质量比值(W/D)实验,评价敲除TREM2对小鼠肺缺血再灌注后组织损伤、炎症反应以及肺内巨噬细胞焦亡情况的影响.结果:TREM2敲除明显加重了LIRI后肺组织形态学改变,增加肺损伤评分(P＜0.05),升高肺组织湿干质量比值(P＜0.05),促进肺组织炎症因子白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)表达(P＜0.05),增加LIRI后肺组织巨噬细胞焦亡标志物天冬氨酸特异性半胱氨酸蛋白酶-1(caspase-1)和成孔蛋白Gasdermin-D(GSDMD)表达(P＜0.05).结论:TREM2敲除加重LIRI,其机制可能与TREM2缺失引发caspase-1介导的肺内巨噬细胞焦亡有关.
Mechanism of TREM2 knockout aggravating lung ischemia-reperfusion injury in mice
Objective:To investigate the impact and possible regulatory mechanism of triggering receptor ex-pressed on myeloid cells 2(TREM2)in lung ischemia-reperfusion injury(LIRI).Methods:Twelve male C57BL/6J wild-type mice(WT)and twelve TREM2 knockout mice(TREM2 KO)were randomly divided into four groups:WT micesham operation group(WT group),TREM2 KO mice sham operation group(TREM2 KO group),WT mice LIRI group(WT+LIRI group)and TREM2 KO mice LIRI group(TREM2 KO+LIRI group),with 6 mice in each group.The mouse LIRI model was prepared by occluding the hilum of the left lung for 1 h and reperfusion for 24 h in the WT+LIRI group and TREM2 KO+LIRI group,while only the hilum of the lung-was opened without occluding in the chest.Western blotting,immunofluorescence,reverse transcription-quantita-tive PCR(RT-qPCR),hematoxylin-eosin(HE)staining,and lung tissue wet-to-dry weight(W/D)ratio were per-formed to evaluate the impact of TREM2 knockout on tissue injury,inflammation and macrophage pyroptosis af-ter lung ischemia-reperfusion in mice.Results:Knockout of TREM2 significantly exacerbated morphological changes in lung tissue after LIRI,increased lung injury scores(P＜0.05),elevated the W/D ratio of lung tissue(P＜0.05),promoted the expression of inflammatory factors interleukin-1β(IL-1β)and IL-18 in lung tissue after LIRI(P＜0.05),and enhanced the expression of macrophage pyroptosis markers cysteine aspartic acid-specific protease-1(caspase-1)and pore-forming protein Gasdermin-D(GSDMD)in lung tissue after LIRI(P＜0.05).Conclusion:TREM2 knockout can exacerbate LIRI,and its mechanism may be related to caspase-1-mediated py-roptosis of lung macrophages induced by the loss of TREM2.

ischemia-reperfusion injurytriggering receptor expressed on myeloid cells 2pyroptosiscaspase-1pore-forming protein Gasdermin-Dinflammation

郭有缘、梁芳特、刘豪、林飞

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广西医科大学附属肿瘤医院麻醉科,南宁 530021

广西壮族自治区人民医院麻醉科,南宁 530016

广西医科大学第二附属医院麻醉科,南宁 530007

缺血再灌注损伤 2型髓系细胞触发受体 细胞焦亡 天冬氨酸特异性半胱氨酸蛋白酶-1 成孔蛋白Gasdermin-D 炎症反应

国家自然科学基金国家自然科学基金国家自然科学基金广西自然科学基金面上项目广西壮族自治区科学研究与技术开发项目广西数千名中青年骨干教师培养计划广西医学高层次人才培养计划广西医科大学高水平创新团队项目杏湖学者计划

8236002381960022815600182020GXNSFAA159123桂科AB18126061G201903011

2024

10.16190/j.cnki.45-1211/r.2024.02.006

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子：0.788
ISSN：1005-930X
年,卷(期)：2024.41(2)
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