摘要
背景乙醇作为外源性侵袭因素,若持续与胃黏膜接触可引起胃内大量活性氧物质产生进而造成氧化应激损伤.而过氧化物酶体增殖物激活受体α(peroxisome proliferators-activated receptorα,PPARα)对氧化应激具有重要调控效应,在多种相关疾病模型中发挥防治作用.目的探究PPARα对乙醇诱导的慢性胃黏膜损伤是否具有保护作用.方法将小鼠随机分为野生型单纯乙醇饮食(wild-type with ethanol diet,WT-EtOH)组、PPARα敲除型单纯乙醇饮食(PPARα-knockout with ethanol diet,KO-EtOH)组、PPARα敲除型乙醇饮食联合维生素E(PPARα-knockout with ethanol diet combined vitamin E,KO-EtOH+VE)组.喂养16wk后,观察小鼠胃组织病理学改变,检测血清和胃组织中还原型谷胱甘肽(reduced glutathione,GSH)、氧化型谷胱甘肽(oxidized glutathione,GSSG)、丙二醛(malondialdehyde,MDA)的含量,胃组织中4-羟基壬烯醛(4-hydroxynonenal,4-HNE)的表达,胃组织中超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)的活性和mRNA相对表达水平.结果PPARα的缺失加重了乙醇诱导的小鼠胃黏膜病理学损伤,引起血中和胃组织中GSH和GSH/GSSG比值的显著降低,血清和胃组织中MDA的含量及4-HNE的阳性表达上升,并导致胃组织中SOD和CAT的活性以及SOD的mRNA相对表达水平显著降低.应用维生素E后改善了组织病理改变以及CAT的活性和mRNA相对表达水平.结论PPARα缺失引起乙醇诱导的胃黏膜氧化应激损伤加重.
BACKGROUND Ethanol as an exogenous invasive factor,when persistently contacting with the gastric mucosa,can result in the generation of large amounts of reactive oxygen species in the gastric mucosa and cause oxidative stress damage.PPARαhas an important regulatory effect on oxidative stress and plays a preventive role in multiple related disease models.AIM To investigate whether PPARαhas an effect against ethanol-induced chronic gastric mucosal injury.METHODS Mice were randomly divided into three groups:Wild-type mice given an ethanol diet(WT-EtOH),PPARα-knockout mice given an ethanol diet(KO-EtOH),and PPARα-knockout mice given an ethanol diet plus vitamin E(KOEtO H+VE).After feeding 16 wk,gastric histopathological changes were observed.The contents of reduced glutathione(GSH),oxidized glutathione(GSSG),and malondialdehyde(MDA)in serum and gastric tissue,the expression of 4-hydroxynonenal(4-HNE)in gastric tissue,and the activity and mRNA relative expression levels of superoxide dismutase(SOD)and catalase(CAT)in gastric tissue,were detected.RESULTS Loss of PPARαaggravated ethanol-induced gastric mucosal pathological injury in mice,significantly decreased GSH and GSH/GSSG ratio in serum and gastric tissue,increased the content of MDA and the positive expression of 4-HNE,and significantly reduced the activity of SOD and CAT and the relative expression level of SOD mRNA in gastric tissues.Treatment with vitamin E improved gastric mucosal histopathological changes,and the activity and relative expression level of CAT mRNA.CONCLUSION Deficiency of PPARαworsens ethanol-induced oxidative stress injury in the gastric mucosa of mice.
作者
胡晓
郭然
张旭光
Xiao Hu;Ran Guo;Xu-Guang Zhang(Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,Hebei Province,China;The Third General Surgery Department,The Second Affiliated Hospital of Hebei Medical University,Shijiazhuang 050004,Hebei Province,China;Department of Metabolic Regulation,Shinshu University School of Medicine,Matsumoto 390-0803,Nagano,Japan)
出处
《世界华人消化杂志》
CAS
2023年第3期113-120,共8页
World Chinese Journal of Digestology
基金
河北省自然科学基金青年基金资助项目,No.H2020206330。
