摘要
目的:探讨中等强度下坡跑运动对胰岛素抵抗(IR)小鼠非酒精性脂肪肝病(NAFLD)的改善及肝脏巨噬细胞极化的调节作用。方法:C57BL/6N雄性小鼠60只,随机分为正常膳食组和高脂膳食组,干预12周后组内随机分为对照安静组(CON-Sed组)、对照运动组(CON-Ex组)、IR安静组(IR-Sed组)和IR运动组(IREx组)。运动组进行8周最大运动强度45%的中等强度下坡跑运动。干预完成后暴露腹腔,取下肝脏并称取湿重,检测血清生化指标和肝脏TG含量,油红O染色和HE染色进行肝脏病理组织学观察,ELISA方法检测血清中炎症相关蛋白水平,Western blot方法检测肝脏巨噬细胞极化相关蛋白表达,免疫荧光染色检测肝脏巨噬细胞极化标志蛋白表达。结果:1)与CON-Sed组相比:IR-Sed组小鼠腹部脂肪,血清TG、TC和LDL-C水平均明显增加(P<0.01);肝脏颜色发白且肝湿重显著增加(P<0.01);肝细胞体积肿大并填充以弥漫性的脂滴且伴随炎症细胞浸润,脂滴面积显著增加(P<0.01);肝脏TG和血清ALT、AST水平显著增加(P<0.01);促炎因子MCP1、TNFα、IL-1β和IL-6水平显著增高,而抗炎因子IL-10水平显著降低(P<0.01);肝脏中巨噬细胞M1型极化相关蛋白IL-1β、iNOS和CD86表达显著增加,M2型极化相关蛋白IL-10、Arg-1和CD206显著降低(P<0.01)。2)8周下坡跑运动后,与IR-Sed组相比:IR-Ex组小鼠腹部脂肪,血清TG、TC和LDL-C水平均明显降低(P<0.01);肝脏形态改善且肝湿重显著下降(P<0.01);肝细胞脂滴面积显著下降(P<0.01)且炎症细胞浸润减少;肝脏TG和血清ALT、AST水平显著下降(P<0.01);促炎因子MCP1、TNFα、IL-1β和IL-6水平显著下降,而抗炎因子IL-10水平显著增加(P<0.01);肝脏中巨噬细胞M1型极化相关蛋白IL-1β、iNOS和CD86表达显著降低,M2型极化相关蛋白IL-10、Arg-1和CD206表达显著增加(P<0.01)。结论:高脂膳食导致肝脏巨噬细胞M1型极化增加并抑制M2型极化,进而诱导NAFLD的发生发展;中等强度下坡跑改善IR小鼠NAFLD,肝脏巨噬细胞极化的调节可能是其中的重要原因之一。
Objectives:To explore the effect of moderate intensity downhill running on nonalcoholic fatty liver(NAFLD)of insulin resistant(IR)mice and the regulatory effect of liver macrophage polarization.Methods:Sixty C57 BL/6 N male mice were randomly divided into two groups:normal diet group and high fat diet group.After 12 weeks,the mice were randomly divided into control sedentary group(CON-Sed group),control exercise group(CON-Ex group),insulin resistance sedentary group(IR-Sed group)and insulin resistance exercise group(IR-Ex group).In exercise group,the moderate intensity downhill running with the maximum intensity of 45%for 8 weeks was carried out.After 8 weeks of treatments,the liver was removed from the abdominal cavity and weighed.The serum biochemical indexes and liver TG content were measured.The liver histopathology was observed by oil red O and HE staining.The level of inflammation related protein in serum was detected by ELISA,the expression of macrophages polarization related protein in liver was detected by Western blot,and the expression of macrophages polarization markers in liver was detected by immunofluorescence staining.Results:Compared with CON-Sed group,the levels of TG,TC and LDL-C in the serum of IR-Sed group were significantly increased(P<0.01);the color of liver was white and the wet weight was significantly increased(P<0.01);the size of liver cells was enlarged and filled with diffuse lipid droplets,accompanied by inflammatory infiltration,the area of lipid droplets was significantly increased(P<0.01);the levels of liver TG,ALT and AST in serum were significantly increased(P<0.01)The levels of MCP1,TNFα,IL-1β and IL-6 were significantly increased,while IL-10 was significantly decreased(P<0.01);the expressions of IL-1β,iNOS and CD86 in liver were significantly increased,while IL-10,Arg-1 and CD206 were significantly decreased(P<0.01).After 8 weeks of downhill running,compared with IRSed group,TG,TC and LDL-C levels in serum of IR-Ex group decreased significantly(P<0.01);liver morphology improved and wet weight decreased significantly(P<0.01);lipid droplet area and inflammatory infiltration decreased significantly(P<0.01);TG and ALT and AST levels decreased significantly(P<0.01);The level of MCP1,TNFα,IL-1β and IL-6 decreased significantly,while IL-10 increased significantly(P<0.01);the expression of IL-1β,iNOS and CD86 decreased significantly,while IL-10,Arg-1 and CD206 increased significantly(P<0.01).Conclusions:High fat diet increases liver macrophage M1 polarization to induce the development of NAFLD.Moderate intensity downhill running can improve NAFLD of IR mice,and the regulation of liver macrophage polarization may play a key role in this improvement.
作者
艾磊
罗维
袁鹏
刘凌
周越
AI Lei;LUO Wei;YUAN Peng;LIU Ling;ZHOU Yue(Beijing Sport University,Beijing 100084,China;Jiangsu Research Institute of Sports Science,Nanjing 210033,Jiangsu China;Nanjing Sport Institute,Nanjing 210014,Jiangsu China)
出处
《北京体育大学学报》
CSSCI
北大核心
2020年第10期92-103,共12页
Journal of Beijing Sport University
基金
江苏省体育局重大体育科研课题(项目编号:ST191103)
江苏省体育科学研究所青年科技人才培养项目(项目编号:2020Q01)
中央高校基本科研业务费专项基金资助课题(项目编号:校2020065)。
作者简介
艾磊,助理研究员,博士研究生,研究方向慢病人群的运动干预;通信作者:周越,教授,博士研究生导师,研究方向运动与机能评定。
