实用医学杂志 ›› 2021, Vol. 37 ›› Issue (13): 1660-1665.doi: 10.3969/j.issn.1006⁃5725.2021.13.003

• 基础研究 • 上一篇    下一篇

匹立尼酸对肝癌经导管动脉栓塞术后癌旁肝组织氧化应激和细胞凋亡的作用

杨培鈺1, 杜伟2, 李正亮2, 周舟2, 熊文翠1   

  1. 大理大学1 临床医学院,2 第一附属医院放射科(云南大理 671000)

  • 出版日期:2021-07-10 发布日期:2021-07-10
  • 通讯作者: 杜伟 E⁃mail:2393350136@qq.com
  • 基金资助:

    国家自然科学基金地区项目(编号:81660300)

Effect of WY⁃14643 on oxidative stress and apoptosis of liver tissues adjacent to cancer after TAE

YANGPeiyu,DU Wei,LI Zhengliang,ZHOU Zhou,XIONG Wencui.    

  1. School of Clinical Medicine,Dali University,Da⁃li 671000,China

  • Online:2021-07-10 Published:2021-07-10
  • Contact: DU Wei E⁃mail:2393350136@qq.com

摘要:

目的 探讨过氧化物酶体增殖物激活受体⁃α激动剂(PPAR⁃α激动剂)匹立尼酸(WY⁃14643)对肝癌经导管动脉栓塞术(transcatheter arterial embolization,TAE)后癌旁肝组织氧化应激和细胞凋亡的作用。方法 成功建立兔 VX2 肝癌模型 60 只,随机分为对照组(CON 组)、TAE 组、联合治疗组(WT 组),每组 20 只,TAE 组进行 TAE 手术治疗,WT 组在 TAE 术前连续 3 d 经耳缘静脉注入 3 mg/(kg·d)WY⁃14643,对照组不作任何处理。术后经耳缘静脉抽取外周血 4 mL 测量肝功能指标 ALT、AST;化学发光法检测氧化应激指标 SOD、GSH⁃Px、CAT、MDA;TUNEL 法检测肝细胞凋亡情况,计算凋亡指数(apoptotic index,AI);RT⁃qPCR Western blot 法检测癌旁肝组织 SOD1、Bcl⁃2、Caspase⁃3 mRNA 和蛋白的相对表达情况。结果TAE 组肝功能指标、MDA 含量、AI Caspase⁃3 表达明显增高,SOD、GSH⁃Px、CAT 活性和 SOD1、Bcl⁃2 表达明显降低;WT 组各数据与 TAE 组相反(P<0.05)。结论 PPAR⁃α激动剂匹立尼酸可以增强抗氧化酶SOD、GSH⁃Px、CAT 的活性并增加 SOD1 的表达来抑制氧化应激,增加 Bcl⁃2 和减少 Caspase⁃3 表达来减少细胞凋亡,从而使得TAE 术后癌旁肝组织肝功能损伤得到改善。

关键词:

肝癌, 经导管动脉栓塞术, 匹立尼酸, 过氧化物酶体增殖物激活受体, 氧化应激, 细胞凋亡

Abstract:

Objective To investigate the effect of pirinixic acid(WY⁃14643),the peroxidase proliferator⁃activated receptor⁃alpha agonist(PPAR⁃α agonist),on oxidative stress and apoptosis of parahepatic tissues in livercancer after transcatheter arterial embolization(TAE). Methods VX2 liver cancer model with 60 rabbits weresuccessfully established,the rabbits randomly divided into three groups:the control,TAE and combined treatment(WT),20 in each. The TAE group was treated with TAE operation,the WT group with injection of WY⁃14643[3 mg/(kg·d)]through the ear vein for 3 consecutive days before TAE,and the control group did not receive anytreatment. After operation,4ml of peripheral blood was drawn from the ear vein for examinations of liver functionindicators ALT and AST,followed by detection of oxidative stress indicators SOD,GSH⁃Px,CAT and MDA usingchemiluminescence,detection of apoptosis of the liver cells and calculation of the apoptotic index (AI)usingTUNEL,and detection of the mRNA and protein expressions of SOD1,Bcl⁃2 and caspase⁃3 using RT⁃qPCR andWestern blot. Results The liver function indexes,MDA content and expressions of AI and Caspase⁃3 in the TAEgroup were significantly increased,and the SOD,GSH⁃Px,CAT activity and expressions of SOD1 and Bcl⁃2 inthe TAE group were significantly decreased. The data in the WT group were opposite the TAE group(P < 0.05).Conclusion PPAR⁃ α agonist pirinixic acid can inhibit oxidative stress by enhancing the activity of antioxidantenzymes SOD,GSH ⁃Px and CAT and enhancing the expressions of SOD1,reduce cell apoptosis by upregulatingthe expression of Bcl⁃2 and downregulating the expression of Caspase⁃3,so that the damage to liver tissues adja⁃cent to cancer after TAE can be mitigated.

Key words:

liver cancer, transcatheter arterial embolization, WY ?14643, peroxisome proliferatorsactivated receptor?α, oxidative stress, apoptosis