摘要
目的:探讨转化生长因子β激活激酶-1(TAK1)在非酒精性脂肪性肝病(NFALD)中的作用及其对巨噬细胞极化的影响。方法:将80只5~6周龄C57BL/6雄性小鼠随机分为对照组、模型组、低剂量组和高剂量组。其中,对照组小鼠给予正常饮食,模型组小鼠给予高脂饮食,低剂量和高剂量组小鼠在高脂饮食的基础上,每周腹腔注射1 mg/kg和5 mg/kg的TAK1抑制剂5Z-7-oxozeaenol。持续饲养12周后,HE染色评估肝脏形态。测量小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白(LDL-C)含量。流式细胞术检测小鼠肝脏组织巨噬细胞极化情况。RT-PCR法检测小鼠肝脏组织CD11c、CD206、IL-1β和IL-10 mRNA表达。ELISA检测小鼠肝脏组织IL-1β、IL-10、TNF-α和TGF-β1含量。结果:HE染色结果显示,对照组小鼠肝细胞排列整齐,无脂肪变性和炎症细胞浸润;模型组小鼠肝细胞内可见明显脂肪变性,NAFLD活动度积分显著升高(P<0.05);低剂量组和高剂量组小鼠脂肪变性和炎症细胞显著减少,NAFLD活动度积分明显降低(P<0.05)。与对照组相比,模型组小鼠血清ALT、AST、ALP、TC、TG和LDL-C含量均显著升高,HDL-C含量显著降低(P<0.05);与模型组相比,低剂量组和高剂量小鼠血清ALT、AST、ALP、TC、TG和LDL-C含量显著降低,HDL-C含量显著升高(P<0.05)。与对照组相比,模型组小鼠肝脏组织M1/M2、M1型巨噬细胞标志物CD11c和IL-1βmRNA均明显升高,M2型巨噬细胞标志物CD206和IL-10 mRNA表达降低(P<0.05);与模型组相比,低剂量和高剂量组小鼠肝脏组织M1/M2、CD11c和IL-1βmRNA表达均显著降低,CD206和IL-10 mRNA表达升高(P<0.05)。与对照组相比,模型组小鼠肝脏组织IL-1β和TNF-α表达明显升高,IL-10和TGF-β1表达明显降低(P<0.05);与模型组相比,低剂量和高剂量组小鼠肝脏组织IL-1β和TNF-α表达明显降低,IL-10和TGF
Objective:To investigate the role of transforming growth factorβactivated kinase-1(TAK1)in non-alcoholic fatty liver disease(NFALD)and its influence on macrophage polarization.Methods:Eighty 5~6 weeks C57BL/6 male mice were randomly divided into control group,model group,low-dose group and high-dose group.Among them,mice in control group were given a normal diet,mice in model group were given a high-fat diet,and mice in low-dose and high-dose groups were given 1 mg/kg and 5 mg/kg of TAK1 inhibitor 5Z-7-oxozeaenol per week on the basis of high-fat diet.After 12 weeks of continuous rearing,liver morphology was evaluated by HE staining.Measured contents of mice serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein(LDL-C).Flow cytometry was used to detect the polarization of macrophages in liver tissue of mice.RT-PCR was used to detect expressions of CD11c,CD206,IL-1βand IL-10 mRNA in mice liver tissues.Levels of IL-1β,IL-10,TNF-αand TGF-β1 in liver tissues of mice were detected by ELISA.Results:HE staining showed that the liver cells of control group were arranged neatly without adipocyte degene-ration and inflammatory cell infiltration;obvious steatosis were observed in model group,and the NAFLD activity score was significantly increased(P<0.05);steatosis and inflammatory cells were significantly reduced in both low-dose and high-dose groups of mice,and the NAFLD activity score was significantly reduced(P<0.05).Compared with control group,serum ALT,AST,ALP,TC,TG and LDL-C contents of mice in model group were significantly increased,while HDL-C content was significantly decreased(P<0.05);compared with model group,serum ALT,AST,ALP,TC,TG and LDL-C levels of mice in both low-dose group and high-dose group were significantly reduced,while HDL-C level was significantly increased(P<0.05).Compared with control group,M1/M2,CD11c and IL-1βmRNA expressions were significa
作者
王宇涵
赵莉
吴贵恺
史永红
段惠军
WANG Yuhan;ZHAO Li;WU Guikai;SHI Yonghong;DUAN Huijun(Department of Gastroenterology and Hepatology,Tangshan Gongren Hospital,Tangshan 063000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第9期1829-1833,共5页
Chinese Journal of Immunology
基金
河北省卫健委重点科技研究计划基金项目(20201516)
2019年河北省自然科学基金面上项目(H2019206179)。
关键词
转化生长因子β激活激酶-1
非酒精性脂肪性肝病
巨噬细胞极化
炎症
Transforming growth factorβactivated kinase-1
Non-alcoholic fatty liver disease
Macrophage polarization
Inflammation
