TREM-1抑制剂对肥胖哮喘小鼠气道炎症的影响

EFFECT OF TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-1 INHIBITOR ON AIRWAY INFLAMMATION IN OBESE ASTHMATIC MICE

目的探讨髓样细胞触发受体1(TREM-1)抑制剂LR12对肥胖哮喘小鼠气道炎症的影响。方法将40只雌性C57BL/6J小鼠随机分为对照组(A组)、哮喘组(B组)、肥胖哮喘组(C组)、LR12处理肥胖哮喘组(D组)和地塞米松处理肥胖哮喘组(E组)。计算各组小鼠支气管肺泡灌洗液(BALF)中的白细胞总数和中性粒细胞比例,苏木精-伊红(HE)染色观察小鼠肺组织炎症损伤情况,采用酶联免疫吸附试验(ELISA)法测定小鼠血清白细胞介素6(IL-6)和白细胞介素17A(IL-17A)的水平,实时荧光定量PCR(qPCR)法检测小鼠肺组织TREM-1、IL-17A的mRNA表达水平,蛋白印迹法测定小鼠肺组织Nod样受体蛋白3(NLRP3)、Caspase-1p20和白细胞介素1β(IL-1β)蛋白的表达。结果与A组比较,B组和C组小鼠出现气道损伤和炎性细胞浸润增多,BALF中白细胞总数和中性粒细胞比例、血清IL-6和IL-17A表达、肺组织TREM-1和IL-17A的mRNA表达以及NLRP3信号通路相关蛋白表达水平均明显升高,且C组上述指标变化更明显,而D组上述指标较C组均有改善,差异具有统计学意义(F=22.190~59282.000,P<0.05)。与D组不同,E组小鼠BALF中的中性粒细胞比例较C组无明显变化(P>0.05)。结论TREM-1抑制剂LR12可能通过减少NLRP3激活来减轻肥胖哮喘小鼠的气道炎症。

Objective To investigate the effect of triggering receptor expressed on myeloid cells-1(TREM-1)inhibitor LR12 on airway inflammation in obese asthmatic mice.Methods A total of 40 female C57BL/6J mice were randomly divided into control group(group A),asthma group(group B),obese asthma group(group C),LR12-treated obese asthma group(group D),and dexamethasone-treated obese asthma group(group E).Total leukocyte count and neutrophil percentage in bronchoalveolar lavage fluid(BALF)were calculated for each group,and HE staining was used to observe the inflammatory injury of lung tissue.ELISA was used to measure the serum levels of interleukin-6(IL-6)and interleukin-17A(IL-17A),quantitative real-time PCR was used to measure the mRNA expression levels of TREM-1 and IL-17A in lung tissue,and Western blot was used to measure the protein expression levels of NOD-like receptor protein3(NLRP3),Caspase-1p20,and interleukin-1β(IL-1β)in lung tissue.Results Compared with group A,group B and group C had significant increases in airway injury,inflammatory cell infiltration,total leukocyte count and neutrophil percentage in BALF,serum levels of IL-6 and IL-17A,mRNA expression levels of TREM-1 and IL-17A in lung tissue,and expression levels of proteins associated with the NLRP3 signal pathway,and group C had significantly greater changes than group B,while compared with group C,group D had significant improvements in the above indices(F=22.190-59282.000,P<0.05).Compared with group C,group E had no significant change in neutrophil percentage in BALF(P>0.05).Conclusion The TREM-1 inhibitor LR12 may alleviate airway inflammation in obese asthmatic mice by reducing NLRP3 activation.