巨噬细胞调控肝脏脂代谢促进日本血吸虫性肝损伤作用机制研究  

Macrophages regulate liver lipid metabolism to promote liver injury caused by Schistosoma japonicum infection

作　　者：李静 张蓓蓓 颜超 吴忠道 郑葵阳 LI Jing;ZHANG Bei-bei;YAN Chao;WU Zhong-dao;ZHENG Kui-yang(Department of Pathogenic Biology and Immunology,Xuzhou Medical University,Jiangsu Key Laboratory of Immunology and Metabolism,Jiangsu 221004,China;Department of Parasitology,Zhongshan School of Medicine,Sun Yat-sen University,Key Laboratory of Tropical Diseases Prevention and Control,Ministry of Education,Sun Yat-sen University)

机构地区：[1]徐州医科大学病原生物学与免疫学教研室江苏省免疫与代谢重点实验室,江苏徐州221004 [2]中山大学中山医学院寄生虫学教研室中山大学热带病防治研究教育部重点实验室

出　　处：《中国病原生物学杂志》2022年第3期278-282,共5页Journal of Pathogen Biology

基　　金：江苏省自然科学基金项目(No.BK20201011);江苏省高校自然科学研究项目(No.20KJB310011);江苏省博士后基金项目(No.RC7062005);江苏省研究生科研创新计划(No.KYCX20-2468)。

摘　　要：目的研究巨噬细胞通过调控肝脏脂代谢抑制日本血吸虫感染所致肝损伤的作用机制。方法18只清洁级BALB/c雄性小鼠随机分为健康对照组(Control组)、PBS处理感染组(Infected-PBS组)及巨噬细胞清除剂处理感染组(Infected-LipClod组),其中感染组小鼠每只经肤感染(15±1)条日本血吸虫尾蚴。在感染的第28 d采用流式细胞术检测巨噬细胞清除效率;取小鼠肝脏制片,采用HE染色和Masson染色检测肝脏虫卵肉芽肿面积以及纤维化情况;采集小鼠血,分离血清,采用自动生化分析仪检测甘油三酯(Triglyceride,TG)和胆固醇(Cholesterol,CHOL)含量,采用qRT-PCR检测脂质代谢相关基因转录水平。结果流式细胞检测Infected-PBS组巨噬细胞含量为28.45%,Infected-LipClod组巨噬细胞含量为8.25%,差异有统计学意义(t=4.681,P<0.01)。表明LipClod脂质体可有效清除肝脏巨噬细胞。与Infected-PBS组相比,Infected-LipClod组小鼠肝脏色泽红润、虫卵结节数量显著减少;HE与Masson染色显示,Infected-LipClod组小鼠肝脏肉芽肿数量及面积均显著减少,纤维化病变减轻(t值分别为5.661,7.686,2.708,P<0.05或P<0.01)。与Control组相比,Infected-PBS组小鼠血清中TG和CHOL含量降低(F值分别为12.959和43.764,均P<0.01),肝脏脂代谢合成基因表达下调(F=55.463,P<0.01),分解代谢相关基因CPT1和CD36 mRNA表达上调,FABP mRNA下调(F值分别为13.460,123.674,11.282,均P<0.001),而Infected-LipClod组小鼠血清TG以及CHOL含量出现回升趋势(F值分别为12.959,43.764,均P<0.01),肝脏脂代谢合成基因FASN,ACC1和ACLY的mRNA表达升高(F值分别为22.765,26.319,55.463,均P<0.01),分解代谢相关基因表达降低(F=123.674,P<0.01)。结论巨噬细胞可通过调控肝脏脂质代谢进而促进日本血吸虫感染所致的肝损伤过程。Objective To clarify the mechanism that macrophages inhibit liver injury caused by Schistosoma japonicum infection via regulating liver lipid metabolism.Methods Eighteen BALB/c male mice of clean-grade were randomly divided into Control group,Infected group treated with PBS(Infected-PBS group),Infected group treated with macrophage scavenger(Infected-LipClod group).Each mouse in the infected group was infected with(151)S.japonicum cercariae.On the 28 th day of infection,the depleted efficiency of macrophages was detected by flow cytometry.HE staining and Masson staining were used to detect hepatic granulomatous reaction and fibrosis formation.Blood was collectedfor detecting triglyceride(TG)and cholesterol(CHOL)levels by automated biochemical analyzer.Transcription levels of genes related to lipid metabolism were detected by qRT-PCR.Results The ratio of macrophages was 28.45%in the Infected-PBS group and 8.25%in the Infected-LipClod group,The difference between these groups is statistically significant(The t-values are4.681,P<0.01),which indicated that macrophages were depleted by LipClod liposomes effectively.Compared with the Infected-PBS group,the liver was ruddy,and the number of egg nodules was decreased significantly in Infected-LipClod group.HE and Masson stanings showed that the number and area of liver granuloma all decreased significantly in the Infected-LipClod group,and the fibrosis also decreased significantly(The t-values are 5.661,7.686,2.708,P<0.05 or P<0.01).Compared with the Control group,the serum TG and CHOL levels in the Infected-PBS group were decreased(The F-values are 12.959 and 43.764,P<0.01).In addition,the lipid biosynthesis related genes were decreased(The F-values are 55.463,P<0.01).The lipid catabolism related genes CPT1 and CD36 mRNA expression were increased,and FABP mRNA was decreased(The F-values are 13.460,123.674,11.282,P<0.001).However,in comparison with the control group,the serum levels of TG and CHOL increased in Infected-LipClod group(The F-values are 12.959,The F-values a

关 键 词：巨噬细胞 脂代谢 日本血吸虫 肝损伤 

分 类 号：R383.24[医药卫生—医学寄生虫学]