摘要
目的探究GLPG1205对脓毒症诱导的急性肺损伤的改善作用及其介导GPR84调节巨噬细胞极化发挥作用的机制。方法C57BL/6小鼠随机分为假手术组(Sham组)、脓毒症模型组(CLP组)和GLPG1205治疗组(GLPG1205组),每组10只,采用盲肠结扎穿刺(CLP)法建立小鼠脓毒症模型。HE染色观察小鼠肺组织病理损伤;检测小鼠肺组织湿干重比;TUNEL染色观察小鼠肺组织细胞凋亡情况;ELISA检测小鼠血清和BALF中炎性因子水平;流式细胞术检测小鼠肺组织中M1/M2型巨噬细胞比例;RT-qPCR检测小鼠肺组织中GPR84 mRNA表达;Western blot检测肺组织中NLRP3炎症小体相关蛋白表达。结果GLPG1205治疗改善CLP小鼠肺组织病理损伤,降低肺组织湿干重比和细胞凋亡水平以及血清和BALF中IL-6、TNF-α和IL-1β水平,降低CLP小鼠肺组织中M1型巨噬细胞比例,并增加M2型巨噬细胞比例。GLPG1205治疗未能降低CLP诱导的肺组织中GPR84表达,但下调CLP小鼠肺组织中NLRP3、ASC和cleaved caspase1蛋白表达。结论GLPG1205改善CLP诱导的小鼠急性肺损伤,其机制与抑制GPR84介导的NLRP3炎症小体激活改善CLP诱导的小鼠肺组织M1/M2型巨噬细胞失衡有关。
Objective To explore the improvement effect of GLPG1205 on sepsis-induced acute lung injury and the mechanism of GPR84 regulating macrophage polarization.Methods C57BL/6 mice were randomly divided into sham group(Sham group),sepsis model group(CLP group)and GLPG1205 treatment group(GLPG1205 group),with 10 mice in each group.Mouse sepsis model was established by cecal ligation and puncture(CLP).HE staining was used to observe the pathological injury of lung tissue in mice.The wet dry weight ratio of lung tissue of mice was detected and the apoptosis of cells in lung tissue of mice was observed by TUNEL staining.ELISA was used to detect the levels of inflammatory factors in serum and BALF of mice.Flow cytometry was used to detect the ratio of M1/M2 macrophages in lung tissues of mice.RT qPCR was used to detect the expression of GPR84 mRNA in lung tissues of mice,and Western blot was used to detect the expressions of NLRP3 inflammasome related proteins in lung tissues of mice.Results GLPG1205 treatment improved the pathological injury of lung tissue in CLP mice,decreased the wet dry weight ratio and apoptosis of cells in lung tissue,and the levels of IL-6,TNF-α and IL-1β in serum and BALF,decreased the proportion of M1 type macrophages and increased the proportion of M2-type macrophages in lung tissues of CLP mice.GLPG1205 treatment failed to reduce the expression of GPR84 in CLP induced lung tissue,but down-regulated the expressions of NLRP3,ASC and cleaved caspasel proteins in lung tissues of CLP mice.Conclusion GLPG1205 improves acute lung injury induced by CLP in mice,and the mechanism is related to the inhibition of NLRP3 inflammasome activation mediated by GPR84,which improves the imbalance of M1/M2-type macrophages in mouse lung tissue induced by CLP.
作者
张慧璠
张飞燕
吕洁
郭宏鹏
ZHANG Hui-fan;ZHANG Fei-yan;LV Jie;GUO Hong-peng(Department of Intensive Care Medicine,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004;Human Stem Cell Institute,General Hospital of Ningxia Medical University,Yinchuan 750004;Department of Medical Laboratory Center,The Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi 830011;Department of General Surgery,The Second Hospital Affiliated to Shenyang Medical College,Shenyang 110002,China)
出处
《解剖科学进展》
2025年第5期683-686,690,共5页
Progress of Anatomical Sciences
基金
辽宁省科学技术计划重大科研项目(2022JH2/101300035)。
