小鼠急性肝损伤对棕色脂肪组织功能的影响及机制研究  

Effects of acute liver injury on brown adipose tissue function and associated mechanisms in mice

作　　者：冯妙 卜浩林 李丽红 郭林芝[2] 苗宇船 郭建红[1] FENG Miao;BU Haolin;LI Lihong;GUO Linzhi;MIAO Yuchuan;GUO Jianhong(Department of Pathophysiology,Shanxi Medical University,Taiyuan 030001,China;Laboratory of Morphology,Shanxi Medical University,Taiyuan 030001;School of Basic Medicine,Shanxi University of Traditional Chinese Medicine,Jinzhong 030619)

机构地区：[1]山西医科大学病理生理学教研室,太原030001 [2]山西医科大学形态学实验室,太原030001 [3]山西中医药大学基础医学院,山西晋中030619

出　　处：《中国比较医学杂志》2020年第4期63-69,共7页Chinese Journal of Comparative Medicine

基　　金：教育部产学合作协同育人项目(201802268015);山西中医药大学“肝脏炎性疾病中西医结合基础研究创新团队”资助项目(2018TD-016)。

摘　　要：目的探讨四氯化碳(CCl4)诱导的急性肝损伤小鼠在不同时间点对棕色脂肪组织的影响及相关机制。方法18只8周龄C57BL/6雄性小鼠随机分为对照组、CCl42周组、CCl44周组,每组6只,CCl4组注射CCl42次,对照组给予同剂量橄榄油。称重棕色脂肪组织;HE染色观察肝和棕色脂肪组织的病理变化;免疫组织化学和实时定量PCR检测棕色脂肪组织解偶联蛋白1(UCP1)的表达;酶联免疫吸附测定(ELISA)法检测血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)和肿瘤坏死因子-α(TNF-α)的含量;Pearson法检验Ucp1 mRNA水平与TNF-α含量间的关系。结果与对照组相比,CCl42周组血清ALT、AST含量增多(P<0.01),棕色脂肪组织重量减少(P<0.05),UCP1蛋白表达减少(P<0.05),Ucp1 mRNA表达减少(P<0.05),血清中TNF-α含量增多(P<0.001);与CCl42周组相比,CCl44周组血清中ALT、AST含量减少(P<0.05),棕色脂肪组织重量增加(P<0.05),Ucp1 mRNA表达增多(P<0.01),血清中TNF-α含量减少(P<0.001);CCl42周组和CCl44周组Ucp1 mRNA水平与TNF-α含量均呈显著负相关(r=-0.950,P<0.01;r=-0.859,P<0.05)。结论急性肝损伤可导致棕色脂肪组织功能下降,机体产热减少,从而影响代谢稳态,机制可能与TNF-α含量升高有关。Objective To investigate the effects of carbon tetrachloride(CCl4)-induced acute liver injury on brown adipose tissue at different time points and to evaluate the related mechanisms.Methods Eighteen 8-week-old C57 BL/6 male mice were randomly divided into a control group,CCl42-week group,and CCl44-week group,with 6 rats in each group.CCl4 group was injected with CCl4 twice,and the control group was given the same dose of olive oil.Brown adipose tissue was then weighed,and HE staining was used to observe pathological changes in the liver and brown adipose tissue.Immunohistochemistry and real-time quantitative PCR were used to detect the expression of uncoupling protein 1(UCP1)in brown adipose tissue.The enzyme-linked immunosorbent assay(ELISA)method was used to evaluate levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and tumor necrosis factor-α(TNF-α)in serum.The Pearson method was used to test the relationship between Ucp1 mRNA levels and TNF-αcontent.Results Compared with the control group,the serum content of ALT and AST in the CCl42-week group were increased(P<0.01),the weight of brown adipose tissue in the CCl42-week group was decreased(P<0.05),the expression of UCP1 protein in brown adipose tissue in the CCl42-week group was decreased(P<0.05),the expression of Ucp1 mRNA in the CCl42-week group was decreased(P<0.05),and the serum content of TNF-αin the CCl42-week group was increased(P<0.001).Compared with the CCl42-week group,the serum content of ALT and AST in the CCl44-week group was decreased(P<0.05),the weight of brown adipose tissue in the CCl44-week group was increased(P<0.05),the expression of Ucp1 mRNA in the CCl44-week group was increased(P<0.01),and the serum content of TNF-αin the CCl44-week group was decreased(P<0.001).There was a significant negative correlation between Ucp1 mRNA levels and TNF-αcontent in the CCl42-week group and the CCl44-week group(r=-0.950,P<0.01;r=-0.859,P<0.05).Conclusions Acute liver injury can lead to the decrease of brown adipose tissue func

关 键 词：棕色脂肪组织 解偶联蛋白1 肝损伤 肿瘤坏死因子-Α 

分 类 号：R-33[医药卫生]