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引用本文:杨惠,陈永鑫,任鹏艳,文波,甘诗泉,沈祥春,李悦.基于PINK1/Parkin/铁死亡信号探讨艳山姜挥发油防治糖尿病肾病的机制研究[J].中国现代应用药学,2024,41(17):12-19.
Yang hui,Chen Yonxin,Ren pengyan,Wenbo,Gan shiquan,Shen xiangchun,Li yue.Essential oil from?fructus alpiniae zerumbet alleviates diabetic nephropathy through PINK1/ Parkin/ferroptosis signal pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(17):12-19.
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基于PINK1/Parkin/铁死亡信号探讨艳山姜挥发油防治糖尿病肾病的机制研究
1, 杨惠2, 陈永鑫3, 任鹏艳3, 文波3, 甘诗泉3, 沈祥春3, 李悦1
1.贵阳市妇幼保健院;2.济宁医学院;3.贵州医科大学
摘要:
摘要:目的 基于PINK1/Parkin/铁死亡信号探究艳山姜挥发油(EOFAZ)调控糖尿病肾病机制。方法 高糖高脂饲料(HFSD)饲养联合腹腔注射链脲佐菌素(STZ)建立2型糖尿病小鼠(T2DM)模型,给予EOFAZ进行干预,实验分组为:正常对照组(C),糖尿病组(DM),DM+EOFAZ低剂量组(90 mg·kg -1),DM+EOFAZ高剂量组(180 mg·kg -1),DM+铁死亡抑制剂组(Ferrostatin-1,5 mg·kg -1),EOFAZ毒性组(180 mg·kg -1)。EOFAZ组、Ferrostatin-1组分别灌胃EOFAZ和Ferrostatin-1,其余组以生理盐水灌胃,每日灌胃一次,持续8周后,分析血糖指标。HE、PAS染色对肾组织进行形态学观察;免疫印迹分析线粒体自噬关键蛋白PINK1及Parkin的表达;免疫印迹分析及免疫组织化学分析铁死亡标志蛋白GPX4及COX2的表达;组织铁试剂盒检测组织的铁含量;生化试剂盒分析肾组织中SOD、GSH及MDA的水平。结果 与DM组比较,给予EOFAZ后可明显改善肾组织病理学变化;显著上调PINK1、Parkin及GPX4的表达,下调COX2的表达;降低肾组织铁含量;增加SOD活性及GSH含量,降低MDA水平。其中EOFAZ毒性组中各指标与正常对照组相当,无明显差异。
关键词:  EOFAZ  糖尿病肾病  PINK1- Parkin信号  铁死亡
DOI:
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基金项目:贵州省科技计划项目(黔科合基础-ZK[2022]一般 005);国家自然科学( No.82060772);贵阳市高层次创新型青年卫生人才培养计划项目,[2022]筑卫健科合同字第005号;贵州省中医药管理局中医药、民族医药科学技术研究课题项目(QZYY-2022-032)
Essential oil from?fructus alpiniae zerumbet alleviates diabetic nephropathy through PINK1/ Parkin/ferroptosis signal pathway
1, Yang hui2, Chen Yonxin3, Ren pengyan3, Wenbo3, Gan shiquan3, Shen xiangchun3, Li yue1
1.Guiyan maternal and Child Health Hospital;2.Jining Medical University;3.Guizhou Medical University
Abstract:
ABSTRACT: OBJECTIVE To explore the mechanism of diabetes nephropathy regulated by essential oil from?fructus alpiniae zerumbet(EOFAZ) based on PINK1/Parkin/ferroptosis. METHODS type 2 diabetes mice (DM) was established by feeding high sugar and high fat diet (HFSD) and intraperitoneal injection of streptozotocin (STZ). The mice were given EOFAZ for intervention. DM mice were randomly divided into normal group (C), diabetes group (DM), DM+E-L (90 mg·kg-1), DM+E-H (180 mg·kg-1), DM+ferroptosis inhibitor group (Ferrostatin-1, 5 mg·kg-1), EOFAZ toxicity group (180 mg·kg-1). The EOFAZ group and Ferrostatin-1 group were given EOFAZ and Ferrostatin-1, respectively. At the same time, the normal group and DM group were given equal volume of physiological saline once a day for 8 weeks, the mice were sacrificed, blood was collected to measured fasting blood glucose. HE and PAS staining were used to observe the morphology of renal tissue; Immunoblotting analysis of the expression of mitochondrial autophagy key proteins PINK1 and Parkin; Immunoblotting and immunohistochemistry analysis were used to investigate the expression of ferroptosis marker proteins GPX4 and COX2; The iron assay kit detects the iron content of the renal tissue; ELISA kit was used to analyze the levels of SOD, GSH, and MDA in renal tissue.RESULTS Compared with DM, EOFAZ could significantly improve the renal histopathology changes; Significantly upregulated the expression of PINK1, Parkin, and GPX4, and downregulated the expression of COX2; Reduce iron content in renal tissue; Increase SOD activity and GSH content, reduce MDA levels.And there were no significant difference between the normal control group and EOFAZ toxicity group in those results . CONCLUSION EOFAZ can significantly improve diabetes nephropathy, which may be related to the regulation of PINK1/ Parkin /ferroptosis. KEY WORDS: EOFAZ; Diabetes nephropathy; PINK1- Park signal; ferroptosis
Key words:  EOFAZ  Diabetes nephropathy  PINK1- Park signal  ferroptosis
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