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  

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

作　　者：杨培鈺 杜伟 李正亮 周舟 熊文翠 YANG Peiyu;DU Wei;LI Zhengliang;ZHOU Zhou;XIONG Wencui(School of Clinical Medicine,Dali University,Dali 671000,China)

机构地区：[1]大理大学临床医学院,云南大理671000 [2]大理大学第一附属医院放射科,云南大理671000

出　　处：《实用医学杂志》2021年第13期1660-1665,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金地区项目(编号:81660300)。

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和Western blot法检测癌旁肝组织SOD1、Bcl-2、Caspase-3的mRNA和蛋白的相对表达情况。结果TAE组肝功能指标、MDA含量、AI和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。Objective To investigate the effect of pirinixic acid(WY-14643),the peroxidase proliferatoractivated receptor-alpha agonist(PPAR-αagonist),on oxidative stress and apoptosis of parahepatic tissues in liver cancer after transcatheter arterial embolization(TAE).Methods VX2 liver cancer model with 60 rabbits were successfully 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 any treatment.After operation,4ml of peripheral blood was drawn from the ear vein for examinations of liver function indicators ALT and AST,followed by detection of oxidative stress indicators SOD,GSH-Px,CAT and MDA using chemiluminescence,detection of apoptosis of the liver cells and calculation of the apoptotic index(AI)using TUNEL,and detection of the mRNA and protein expressions of SOD1,Bcl-2 and caspase-3 using RT-qPCR and Western blot.Results The liver function indexes,MDA content and expressions of AI and Caspase-3 in the TAE group were significantly increased,and the SOD,GSH-Px,CAT activity and expressions of SOD1 and Bcl-2 in the TAE group were significantly decreased.The data in the WT group were opposite the TAE group(P<0.05).Conclusion PPAR-αagonist pirinixic acid can inhibit oxidative stress by enhancing the activity of antioxidant enzymes SOD,GSH-Px and CAT and enhancing the expressions of SOD1,reduce cell apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Caspase-3,so that the damage to liver tissues adjacent to cancer after TAE can be mitigated.

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-Α 氧化应激 细胞凋亡 

分 类 号：R73-361[医药卫生—肿瘤] R735.7[医药卫生—临床医学]