PPARγ在结核分枝杆菌感染小鼠脂质代谢中的作用

Effects of PPARγ/CD36 pathway on lipid metabolism in mice infected with Mycobacterium tuberculosis

目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)/CD36通路对结核分枝杆菌(MTB)感染小鼠脂质代谢的影响。方法:使用结核分枝杆菌毒株H37Rv,建立小鼠感染模型。实验分为对照组、MTB组、MTB+罗格列酮组和MTB+GW9662组。收集各组肺组织标本,检测感染小鼠肺组织荷菌量;分别采用RT-qPCR和Western blot法检测肺组织中PPARγ的mRNA和蛋白表达;采用免疫组织化学法检测肺组织CD36的表达;采用油红O染色检测肺组织脂质水平;HE染色后于普通显微镜下观察肺组织病理变化;收集各组血液标本,采用酶联免疫吸附法检测血浆中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的水平。结果:MTB显著升高小鼠肺组织PPARγ表达(P<0.01)及脂质水平(P<0.05),并诱导CD36表达,但降低小鼠血浆脂质浓度(P<0.05);PPARγ激动剂罗格列酮能够增强MTB所诱导的肺组织脂质水平的升高、血浆脂质浓度的下降及CD36的表达,并且加重肺组织结核性病理改变;PPARγ拮抗剂GW9662则逆转MTB所诱导的上述作用;各组小鼠肺组织PPARγ表达与荷菌量呈正相关(r=0.812,P<0.01)。结论:PPARγ通过CD36途径影响MTB感染小鼠脂质代谢,MTB诱导的PPARγ表达对MTB是一种逃避机体免疫系统对其进行清除的逃逸机制,而这种逃逸与PPARγ活化所致脂质聚集有关。

AIM:To investigate the effect of peroxisome proliferator-activated receptorγ(PPARγ)/CD36 sig-naling pathway on lipid metabolism in mice infected with Mycobacterium tuberculosis(MTB).METHODS:Infective mouse model was established by infecting MTB strain H37 Rv.The experiment was divided into 4 groups:control group,MTB group,MTB+rosiglitazone group and MTB+GW9662 group.The mouse lung tissues were collected to detect the bac-terial load.RT-qPCR and Western blot were used to determine the expression of PPARγat mRNA and protein levels.Im-munohistochemistry was used to detect the expression of CD36.Oil red O staining was used to detect the lipid level.HE staining was used to observe the pathological changes.Blood samples were collected and the levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured by ELISA.RESULTS:MTB significantly increased the expression of PPARγ(P<0.01)and lipid level,and induced the expression of CD36,but decreased the plasma lipid concentration.Rosiglitazone,a PPARγagonist,en-hanced the increase of lipid level in the lung tissue,the decrease of plasma lipid concentration and the expression of CD36 induced by MTB,and aggravated the pathological changes of pulmonary tuberculosis.GW9662,a PPARγantagonist,re-versed the above effects of MTB.A positive correlation between the expression of PPARγand the bacteria load was ob-served(r=0.812,P<0.01).CONCLUSION:PPARγaffects lipid metabolism of mice infected with MTB through CD36 pathway.The expression of PPARγis an escape mechanism for MTB to avoid eliminationby immune system,and this es-cape is related to lipid aggregation induced by PPARγactivation.