PPAR-α激动剂WY14643对肝癌TAE术后癌旁肝组织氧化应激的作用

Effect of PPAR-α agonist WY14643 on oxidative stress in liver tissues adjacent to hepatocellular carcinoma after TAE

目的探讨过氧化物酶体增殖物激活受体α(PPAR-α)激动剂WY14643对癌旁肝组织氧化应激损伤的作用及其在肝癌经导管肝动脉栓塞术(TAE)术后对肝功能的保护机制。方法建立兔VX2肝癌模型24只,并随机分为对照组、TAE组、联合治疗组,每组8只。其中TAE组行经导管TAE治疗,联合治疗组连续3 d给予WY14643 3 mg·kg^-1·d^-1后行TAE术,对照组不做处理。检测各组动物TAE术后3 d丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBI)、血清清蛋白(ALB)、凝血酶原时间(PT)。术后3 d后处死动物,分别选取各组动物癌旁组织,采用生化酶学法检测超氧化物歧化酶(SOD)指标、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)和髓过氧化物酶(MPO)水平。结果术后检测肝功能,联合治疗组ALT、AST、TBI降低,ALB升高、PT缩短,与TAE组比较差异有统计学意义(P<0.05)。对照组、TAE组、联合治疗组中SOD水平分别为(46.75±2.09)、(21.24±2.12)、(47.02±2.61)U/mgprot,GSH-PX水平分别为(265.47±5.11)、(190.44±9.78)、(261.91±6.80)U/mgprot,CAT水平分别为(3.48±0.62)、(1.24±0.20)、(3.32±0.64)U/mgprot,MPO水平分别为(160.53±89.18)、(129.76±32.47)、(165.10±82.75)U/mgprot;与TAE组比较,联合治疗组动物的抗氧化指标SOD、GSH-PX、CAT和MPO的活力明显升高,且差异均有统计学意义(P<0.05)。结论PPAR-α激动剂WY14643可减轻TAE术后肝功能损伤,可能与抑制癌旁肝组织氧化应激有关。

Objective To investigate the protective effect of peroxisome proliferator-activated receptor-alpha(PPAR-α)agonist WY14643 on oxidative stress injury of adjacent hepatic carcinoma,and to study the protective mechanism of WY14643 on liver function after transcatheter arterial embolization(TAE)for hepatocellular carcinoma.Methods 24 rabbit were selected after successful inoculation of VX2 hepatocellular carcinoma models.They were divided into three groups randomly:the control group,the TAE group,the combined treatment group with 8 rats in each group.The TAE group was treated with TAE.The combined treatment group was given WY14643 3 mg·kg^-1·d^-1 for three consecutive days and then TAE was performed.The control group received no treatment.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBI),serum albumin(ALB)and prothrombin time(PT)were measured 3 days post-TAE.Para-cancerous tissues were collected from each group.Levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),catalase(CAT)and myeloperoxidase(MPO)were detected by biochemical enzymatic assay.Results Postoperative liver function test showed that ALT,AST and TBI decreased,ALB increased and PT shortened in the treatment group,which was significantly different from that in the TAE group(P<0.05).In the control group,the TAE group and the combined treatment group,biochemical enzymtic assay revealed the concentrations of antioxidant indexes SOD were(46.75±2.09),(21.24±2.12),(47.02±2.61)U/mgprot,the concentrations of GSH-PX were(265.47±5.11),(190.44±9.78),(261.91±6.80)U/mgprot,the concentrations of CAT were(3.48±0.62),(1.24±0.20),(3.32±0.64)U/mgprot,the concentrations of MPO were(160.53±89.18),(129.76±32.47),(165.10±82.75)U/mgprot,respectively.Compared with the TAE group,the activities of antioxidant indexes SOD,GSH-PX,CAT and MPO increased in the treatment group observably,and the changes were statistically significant(P<0.05).Conclusion PPAR-αagonist WY14643 attenuates liver function damage after TAE,which may be related to the inhibition of oxidative stress in liver tissues adjacent to hepatic carcinoma.