中国病理生理杂志2025，Vol.41Issue(9)：1665-1673,9.DOI:10.3969/j.issn.1000-4718.2025.09.001
Ehhadh通过调控脂代谢抑制高脂饮食小鼠肾小管间质炎症
Ehhadh inhibits renal tubulointerstitial inflammation by regulating lipid metabolism in high-fat diet mice
摘要
Abstract
AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.关键词
高脂饮食/烯酰辅酶A水解酶/L-3-羟酰辅酶A脱氢酶/过氧化物酶体/肾小管间质炎症/脂质组学Key words
high-fat diet/enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydrogenase/peroxi-some/tubulointerstitial inflammation/lipidomics分类
医药卫生引用本文复制引用
闫嘉欣,吴婷,朱艳,姚芳,王晓峰,杜春阳..Ehhadh通过调控脂代谢抑制高脂饮食小鼠肾小管间质炎症[J].中国病理生理杂志,2025,41(9):1665-1673,9.基金项目
国家自然科学基金青年基金资助项目(No.82000773) （No.82000773）
河北省自然科学基金资助项目(No.H2022206463) （No.H2022206463）
河北省科技厅中央引导地方科技发展资金项目(自由探索类基础研究)(No.236Z7716G （自由探索类基础研究）
No.236Z7737G) （）
