基础医学与临床 ›› 2023, Vol. 43 ›› Issue (10): 1505-1511.doi: 10.16352/j.issn.1001-6325.2023.10.1505

• 研究论文 • 上一篇    下一篇

PPARα缺失加重乙醇诱导的小鼠胃黏膜慢性损伤

胡晓1*, 郭然2, 张旭光3   

  1. 1.河北医科大学 基础医学院 病理生理学教研室,河北 石家庄 050017;
    2.河北医科大学附属第二医院 普外三科,河北 石家庄 050004;
    3.日本信州大学医学部 代谢调控学研究室,日本 松本 390-0803
  • 收稿日期:2022-12-30 修回日期:2023-05-30 出版日期:2023-10-05 发布日期:2023-10-05
  • 通讯作者: *huhuxiao521@126.com
  • 基金资助:
    河北省自然科学基金(H2020206330)

PPARα-deficiency exacerbates ethanol-induced chronic injury of gastric mucosa in mice

HU Xiao1*, GUO Ran2, ZHANG Xuguang3   

  1. 1. Department of Pathophysiology, School of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China;
    2. the Third Department of General Surgery, the Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050004, China;
    3. Department of Metabolic Regulation, Shinshu University School of Medicine, Matsumoto 390-0803, Japan
  • Received:2022-12-30 Revised:2023-05-30 Online:2023-10-05 Published:2023-10-05
  • Contact: *huhuxiao521@126.com

摘要: 目的 探究过氧化物酶体增殖物激活受体α(PPARα)基因的缺失对长期乙醇诱导的小鼠胃黏膜损伤的影响及作用机制。方法 使用含乙醇的饲料和对照饲料分别喂养野生型和PPARα基因敲除型小鼠,并随机分为4组。饲养16周后,观察小鼠胃组织病理学改变;用ELISA法和RT-qPCR检测血清和胃组织中的炎性因子的含量及表达;用试剂盒检测小鼠血清和胃组织中丙二醛(MDA)的含量;用Western blot法检测小鼠胃内NF-κB信号通路的表达。结果 与乙醇饮食组中的野生型小鼠相比,PPARα敲除小鼠表现出更为严重的胃黏膜损伤, 血中炎性因子TNF-α和IL-1β以及胃组织中MDA的含量明显增多(P<0.05)。胃组织的核p65蛋白表达水平增高(P<0.01),其下游靶基因TNF-α、IL-1β和ICAM-1的mRNA表达水平显著上调(P<0.05)。结论 PPARα缺失引起乙醇诱导的小鼠胃黏膜损伤加重,其机制可能与胃内NF-κB信号通路激活有关。

关键词: 过氧化物酶体增殖物激活受体α, 乙醇, 胃黏膜慢性损伤, NF-κB

Abstract: Objective To investigate the impact and mechanism of peroxisome proliferator-activating receptor α (PPARα) deletion on long-term ethanol-induced gastric mucosal injury in mice. Methods Wild-type and PPARα-knockout mice were treated with ethanol-containing diet and control diet respectively, and randomized into 4 groups. After 16 weeks, the histopathological changes of gastric mucosa were observed. ELISA and RT-qPCR were used to detect the contents and expression of inflammatory factors in serum and gastric tissues. The serum and gastric malondialdehyde(MDA) contents were tested by commercially available kit. Western blot was performed to detect the expression of gastric NF-κB signaling pathway in mice. Results Compared with wild-type mice in ethanol- diet group,PPARα-knockout mice showed more severe gastric mucosal injury and the serum TNF-α,IL-1β and gastric MDA content were significantly increased (P<0.05); The mRNA of the downstream target genes, TNF-α, IL-1β and ICAM-1, were all significantly increased (P<0.05). The level of nuclear protein p65 was increased(P<0.01). Conclusions PPARα-deficiency aggravates ethanol-induced gastric mucosal injury in mice, and the mechanism might be related to the activation of gastric NF-κB signaling pathway.

Key words: PPARα, ethanol, chronic gastric mucosal injury, NF-κB

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