兔VX2肝癌经导管动脉栓塞术后癌旁肝组织氧化应激及细胞凋亡
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摘要
目的观察兔经导管动脉栓塞(TAE)治疗后VX2肝癌模型癌旁肝组织中氧化应激及细胞凋亡情况,探讨其在肝组织损伤中的作用。方法建立25只兔VX2肝癌模型,随机分为TAE组(13只)及对照组(12只),对TAE组行TAE治疗,对照组不做任何处理。于TAE组术后3天及对照组同期检测外周血丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBI)、血清白蛋白(ALB)、凝血酶原时间(PT)。而后处死实验动物,获取肿瘤组织及癌旁肝组织离体标本,用于组织病理检查、生物酶学检测及细胞凋亡检测。以生化酶学方法检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)及过氧化氢酶(CAT);采用TUNEL法检测肝细胞凋亡情况,计算细胞凋亡指数(AI)。结果与对照组比较,TAE组ALT、AST、TBI升高,ALB降低,PT延长;SOD、GSH-PX、CAT均减低(P均<0.001)。TAE组癌旁肝组织可见轻度脂肪变性及大量炎性细胞浸润,对照组癌旁肝组织仅见轻度脂肪变性。TAE组AI为(64.20±2.77)%,明显高于对照组[(2.20±1.90)%;t=-112.30,P<0.001]。结论兔VX2肝癌模型TAE术后肝功能下降可能与癌旁肝组织抗氧化指标活性明显降低,发生氧化应激,导致肝细胞凋亡增多有关。
Objective To observe the oxidative stress and apoptosis of paracancerous liver tissue after transcatheter arterial embolization(TAE)in rabbit models with VX2 hepatocarcinoma,in order to investigate the role of oxidative stress and apoptosis in liver tissue injury.Methods Twenty-five rabbit VX2 hepatocarcinoma models were established and randomly divided into TAE group(n=13)and control group(n=12).TAE group was treated with TAE,while no treatment was performed on control group.Peripheral blood indexes,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBI),serum albumin(ALB)and prothrombin time(PT)were detected three days after operation in TAE group and the same time in control group.Then the experimental animals were killed,and the samples of tumor tissues and paracancerous liver tissues were obtained for histopathological examination,bioenzyme detection and apoptosis detection.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),Catalase(CAT)were detected by biochemical enzymatic assay.The apoptosis of hepatocytes was detected by using TUNEL method,and the apoptotic index(AI)was calculated.Results Compared with control group,ALT,AST and TBI increased,ALB decreased and PT prolonged,while SOD,GSH-PX,CAT decreased in TAE group(all P<0.001).Mild steatosis and inflammatory cell infiltration were observed in paracancerous liver tissue of TAE group,while only mild steatosis was observed in control group.AI of TAE group was significantly higher than that of control group([64.20±2.77]% vs[2.20±1.90]%;t=-112.30,P<0.001).Conclusion The decrease of liver function after TAE in rabbit VX2 hepatocarcinoma models maybe associate with the decrease of antioxidant activity and the oxidative stress which eventually lead to the increase of hepatocyte apoptosis.
Objective To observe the oxidative stress and apoptosis of paracancerous liver tissue after transcatheter arterial embolization(TAE)in rabbit models with VX2 hepatocarcinoma,in order to investigate the role of oxidative stress and apoptosis in liver tissue injury.Methods Twenty-five rabbit VX2 hepatocarcinoma models were established and randomly divided into TAE group(n=13)and control group(n=12).TAE group was treated with TAE,while no treatment was performed on control group.Peripheral blood indexes,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBI),serum albumin(ALB)and prothrombin time(PT)were detected three days after operation in TAE group and the same time in control group.Then the experimental animals were killed,and the samples of tumor tissues and paracancerous liver tissues were obtained for histopathological examination,bioenzyme detection and apoptosis detection.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),Catalase(CAT)were detected by biochemical enzymatic assay.The apoptosis of hepatocytes was detected by using TUNEL method,and the apoptotic index(AI)was calculated.Results Compared with control group,ALT,AST and TBI increased,ALB decreased and PT prolonged,while SOD,GSH-PX,CAT decreased in TAE group(all P<0.001).Mild steatosis and inflammatory cell infiltration were observed in paracancerous liver tissue of TAE group,while only mild steatosis was observed in control group.AI of TAE group was significantly higher than that of control group([64.20±2.77]% vs[2.20±1.90]%;t=-112.30,P<0.001).Conclusion The decrease of liver function after TAE in rabbit VX2 hepatocarcinoma models maybe associate with the decrease of antioxidant activity and the oxidative stress which eventually lead to the increase of hepatocyte apoptosis.
引文
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[13]Wang C,Chen K,Xia Y,et al.N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2pathway.PLoS One,2014,9(9):e108855.
[14]Gil D,Rodriguez J,Ward B,et al.Antioxidant activity of SODand catalase conjugated with nanocrystalline ceria.Bioengineering,2017,4(1):18.
[15]Wang Y,Xiong X,Guo H,et al.ZnPP reduces autophagy and induces apoptosis,thus aggravating liver ischemia/reperfusion injury in vitro.Int J Mol Med,2014,34(6):1555-1564.
[2]Zhang S,Zhang K,Ji P,et al.GABPA predicts prognosis and inhibits metastasis of hepatocellularcarcinoma.BMCCancer,2017,17(1):380.
[3]张成佳,何仕诚,滕皋军,等.TACE治疗原发性肝癌对肝功能影响的相关因素分析.东南大学学报(医学版),2013,32(1):18-22.
[4]Geschwind JF,Kudo M,Marrero JA,et al.TACE treatment in patients with sorafenib-treated unresectable hepatocellular carcinoma in clinical practice:Final analysis of GIDEON.Radiology,2016,279(2):630-640.
[5]Su TS,Lu HZ,Cheng T,et al.Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma>5cm.BMC Cancer,2016,16(1):834.
[6]王君东,胡锦波,杜伟.改良方法建立兔VX2肝癌模型及其MRI表现.医学理论与实践,2013,26(6):701-702.
[7]牛焕章,滕皋军,邓钢,等.兔VX2肝癌模型的影像学表现和栓塞技术的实验研究.中国医学影像技术,2006,22(6):797-800.
[8]徐涛,陈孝平,李丹,等.CD147在兔VX2模型肿瘤组织的表达及意义.中华实验外科杂志,2007,24(1):37-39.
[9]Miki I,Murata S,Uchiyama F,et al.Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy.World J Gastroenterol,2017,23(35):6437-6447.
[10]张靓,杜伟.NF-κB在肝癌介入治疗后癌旁肝细胞中的表达.大理学院学报,2014,213(10):42-46.
[11]Shih SC,Ho TC,Chen SL,et al.Pigment epithelium derived factor peptide protects murine hepatocytes from carbon tetrachloride-induced injury.PLoS One,2016,11(7):e0157647.
[12]李文娟,李明华.间歇低氧对小鼠肝肾组织MDA含量及SOD活力的影响.中国继续医学教育,2016,8(1):66-67.
[13]Wang C,Chen K,Xia Y,et al.N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2pathway.PLoS One,2014,9(9):e108855.
[14]Gil D,Rodriguez J,Ward B,et al.Antioxidant activity of SODand catalase conjugated with nanocrystalline ceria.Bioengineering,2017,4(1):18.
[15]Wang Y,Xiong X,Guo H,et al.ZnPP reduces autophagy and induces apoptosis,thus aggravating liver ischemia/reperfusion injury in vitro.Int J Mol Med,2014,34(6):1555-1564.