南方医科大学学报2024，Vol.44Issue(1)：1-8,8.DOI:10.12122/j.issn.1673-4254.2024.01.01
过表达lncRNA HEM2M改善非酒精性脂肪肝病小鼠的肝脏损伤
Overexpression of lncRNA HEM2M alleviates liver injury in mice with non-alcoholic fatty liver disease
摘要
Abstract
Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.关键词
lncRNA HEM2M/巨噬细胞/非酒精性脂肪肝/细胞焦亡Key words
lncRNA HEM2M/macrophage/non-alcoholic fatty liver disease/pyroptosis引用本文复制引用
孔祥,张腾,张妍,高灵犀,汪文,汪梦燕,王国栋,吕坤..过表达lncRNA HEM2M改善非酒精性脂肪肝病小鼠的肝脏损伤[J].南方医科大学学报,2024,44(1):1-8,8.基金项目
国家自然科学基金(81970699,82072370) （81970699,82072370）
安徽省高校杰出青年科研项目(2022AH020075) （2022AH020075）
弋矶山医院"高峰"培育计划项目(GF2019J04) Supported by National Natural Science Foundation of China(81970699,82072370). （GF2019J04）
