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EPDR1对肝细胞脂质沉积的影响OA北大核心CSTPCD

Effect of EPDR1 on hepatocyte lipid deposition

中文摘要英文摘要

目的:检测室管膜素相关蛋白1(EPDR1)在野生型C57BL/6小鼠各组织中的表达情况;观察2型糖尿病状态下,小鼠各组织中EPDR1的表达;探讨EPDR1对AML12肝细胞脂质沉积的影响.方法:采用Western blot检测C57BL/6小鼠心、肝、脾、肺、肾、腓肠肌、棕色脂肪以及脑组织中EPDR1蛋白的表达;Western blot和免疫组织化学(IHC)染色比较db/db小鼠与C57BL/6小鼠肝、腓肠肌、心和肾组织中EPDR1蛋白表达情况.采用油酸和棕榈酸联合诱导AML12细胞建立脂质沉积模型,且经腺病毒过表达EPDR1和给予外源重组蛋白EPDR1(rEPDR1)干预,ELISA测定胞内甘油三酯(TG)含量,油红O染色评估EPDR1对AML12细胞脂质沉积的影响.结果:Western blot和IHC均显示EPDR1广泛表达于野生型小鼠心、肝、脾、肺、肾、腓肠肌、棕色脂肪和脑组织中,且在肝脏中蛋白表达最高;而在糖尿病db/db小鼠肝、腓肠肌、心和肾组织中较野生型小鼠表达下调;油红O染色结果显示,过表达EPDR1或给予rEPDR1均可减少AML12肝细胞中脂质沉积,且TG含量较模型组下降(P<0.05).结论:EPDR1广泛表达在野生型小鼠各个组织,且在糖尿病小鼠肝脏组织中表达下调,而上调EPDR1可以缓解肝细胞中的脂质沉积.本研究为进一步揭示EPDR1在糖尿病肝组织脂肪变中的作用奠定实验基础.

AIM:This study aims to examine the ependymin-related protein 1(EPDR1)expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes(db/db)mice.The impact of EPDR1 on lipid accumulation in al-pha mouse liver 12(AML12)hepatocytes was also investigated.METHODS:Western blot was used to detect EPDR1 protein expression in the heart,liver,spleen,lung,kidney,gastrocnemius,brown adipose and brain tissues of C57BL/6 mice.Western blot and immunohistochemical(IHC)staining were also used to compare EPDR1 protein expression in the liver,gastrocnemius muscle,heart and kidney tissues of db/db and C57BL/6 mice.To develop an AML12 cell lipid deposi-tion model,palmitic acid(PA)+oleic acid(OA)was used,and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein(rEPDR1).ELISA was conducted to determine intracellu-lar triglyceride(TG)content,and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells.RESULTS:Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tis-sues of wild-type mice,with the liver exhibiting the highest protein expression level.However,EPDR1 expression was down-regulated in the liver,gastrocnemius muscle,heart and kidney tissues in diabetic db/db mice compared with wild-type mice.Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to re-duced lipid accumulation.Furthermore,the TG content significantly decreased compared with the model group(P<0.05).CONCLUSION:EPDR1 is expressed in various tissues of wild-type mice,but showed diminished expression in the liver tissues of diabetic mice.Nevertheless,enhancing the expression of EPDR1 can aid in reducing lipid accumula-tion in hepatocytes.These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue.

王贵芳;常雪冰;扈腊英;刘露;黄亚莉;宋铃榆;周宇霞;郭兵

贵州医科大学病理生理学教研室/贵州省常见慢性疾病发病机制及药物研究重点实验室,贵州 安顺 561113

基础医学

室管膜素相关蛋白12型糖尿病肝细胞脂质沉积

ependymin-related protein 1type 2 diabetes mellitushepatocyteslipid deposition

《中国病理生理杂志》 2024 (007)

1205-1212 / 8

国家自然科学基金资助项目(No.32160207);贵州省科技厅计划项目(黔科合基础-ZK[2021]一般402号);贵州医科大学国家自然科学基金培育项目(No.19NSP040);贵州医科大学优秀青年人才计划(No.2021105)

10.3969/j.issn.1000-4718.2024.07.007

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