摘要
目的探讨恒定自然杀伤T(invariant natural killer T,iNKT)2细胞改善非酒精性脂肪肝(NAFL)肝脂质沉积的机制。方法高脂饮食喂养C57BL/6J小鼠建立NAFL模型。以全自动生化分析仪分析小鼠外周血中血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平。以苏木精-伊红(HE)进行常规肝病理染色。肝iNKT频率及iNKT1、iNKT2亚群频率采用流式细胞术检测。以Western印迹法检测肝脏组织中固醇调节元件结合蛋白1c(SREBP-1c)、过氧化物酶体增殖物激活受体(PPAR)-α、核因子-κB(NF-κB)表达情况。结果与对照组相比,NAFL小鼠体重增加,总胆固醇、HDL-C、LDL-C、ALT水平升高,肝脏脂质沉积增加,肝脏SREBP-1c、PPAR-α蛋白表达升高,NF-κB蛋白磷酸化水平升高(P<0.05或P<0.01)。腹腔注射α-半乳糖基神经酰胺(α-GalCer)后,NAFL小鼠总胆固醇、HDL-C、LDL-C水平降低,肝脂质沉积减少,肝脏SREBP-1c下调,PPAR-α表达上调,肝脏iNKT2亚群比例增加(P<0.05或P<0.01)。结论iNKT2细胞改善NAFL肝脂质沉积与下调肝组织SREBP-1c和上调PPAR-α有关。
Objective To investigate the mechanism of invariant natural killer T(iNKT)2 cell improving hepatic fat deposition in nonalcoholic fatty liver(NAFL).Methods NAFL model was established by feeding C57BL/6J mice with high fat diet.The levels of serum total cholesterol,triglyceride,high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in the peripheral blood of mice were analyzed using automatic biochemical analyzer.The pathological changes of liver were observed with HE staining.The cell frequencies of iNKT,iNKT1,and iNKT2 in liver were detected by flow cytometry.Western blotting was used to detect the expression of sterol regulatory element binding protein 1c(SREBP-1c),peroxisome proliferator activated receptor(PPAR)-α,and nuclear factor-κB(NF-κB)in liver tissues.Results Compared with control group,the body weight of NAFL mice increased,the levels of total cholesterol,HDL-C,LDL-C,ALT,and liver fat deposition increased,the protein expression of SREBP-1c and PPAR-αin liver increased as well as the the protein phosphorylation level of NF-κB.After intraperitoneal injection ofα-galactosylceramide(α-GalCer),the levels of total cholesterol,HDL-C,and LDL-C,liver fat deposition decreased,liver SREBP-1c was down-regulated,PPAR-αexpression was up-regulated,and the proportion of liver iNKT2 subgroup increased in NAFL mice.Conclusion iNKT2 cells improve NAFL liver fat deposition,which is related to the down-regulation of SREBP-1c and up-regulation of PPAR-α.
作者
滕景芳
高翔
王建国
梁蕊
陈冬志
孟明
Teng Jingfang;Gao Xiang;Wang Jianguo;Liang Rui;Chen Dongzhi;Meng Ming(School of Basic Medicial Sciences,Hebei University,Baoding 071000,China;Department of Clinical Laboratory,Affiliated Hospital of Hebei University,Baoding 071000,China;Department of Medical,Hebei University,Baoding 071000,China;Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-Autoimmune Diseases in Hebei Province,Baoding 071000,China)
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2021年第9期813-819,共7页
Chinese Journal of Endocrinology and Metabolism
基金
国家自然科学基金面上项目(81771755)
河北省自然科学基金项目(H2020201022、H2020201300)。
作者简介
通信作者:孟明,Email:mengming127@163.com。
