美洲大蠊提取物对肝癌TAE术后癌旁肝组织SOD、CAT的影响及其机制探讨

The Effect of Periplaneta americana Extract on SOD and CAT in Peritumoral Liver Tissue after TAE and Its Mechanism of Action

摘要: 目的：探讨美洲大蠊提取物对肝癌经导管动脉栓塞(transcatheter arterial embolization, TAE)术后癌旁肝组织SOD、CAT的影响及其机制。方法：前期观测100例原发性肝癌TAE治疗术后患者肝功能水平。后进行动物实验，将通过开腹瘤粒注射法成功建模的36只雄性日本大耳兔随机分为3组，每组12只。对照组用兔VX2肝癌模型，不做处理；TAE组用碘化油栓塞肿瘤供血动脉；美洲大蠊提取物组实验兔从术前3天每天分别以100 mg/kg给药，给药组每日经耳缘静脉给药，给药量均为2 mL/kg，1次/d。免疫组化法检测各组癌旁肝组织PPAR-α、NF-κB的表达水平。生物酶学法检测癌旁肝组织中氧化应激指标SOD、CAT在不同实验组之间的活力变化及癌旁肝组织中NF-κB、SOD1、SOD2、SOD3 mRNA的表达量。结果：前期人群研究中，术前、术后3天、7天、30天的ALT水平分别为(83.89 ± 21.24)、(63.59 ± 21.35)、(57.89 ± 24.24) U/L，AST水平分别为(117.37 ± 27.40)、(86.37 ± 27.53)、(87.52 ± 30.40) U/L，TAE术治疗后3天、7天、30天复查肝功能与术前相比，ALT、AST升高，差异显著(P < 0.05)，术后7天肝功能各指标较术后3天显著改善，一个月后复查肝功能与术前比较，各指标均无显著性差异(P > 0.05)；对照组、TAE组、美洲大蠊提取物组PPAR-α阳性分别为4、2、6只，NF-κB阳性分别为1、9、2只，与对照组、美洲大蠊提取物组比较，TAE组NF-κB阳性率、NF-κB mRNA水平明显升高，与对照组、TAE组比较，美洲大蠊提取物组PPAR-α阳性率、PPAR-αmRNA水平明显升高，差异均有统计学意义(P < 0.05)；术后对照组、TAE组、美洲大蠊提取物组SOD水平分别为(22.48 ± 2.04)、(21.81 ± 0.11)、(25.81 ± 0.23) U/mgprot，CAT水平分别为(1.55 ± 0.19)、(1.15 ± 0.25)、(3.09 ± 0.57) U/mgprot，与对照组、美洲大蠊提取物组比较，TAE组SOD、CAT水平明显降低，与TAE组相比，美洲大蠊提取物组SOD、CAT水平明显提高，差异均有统计学意义(P < 0.05)。结论：美洲大蠊提取物可通过提高抗氧化应激因子即SOD、CAT的活性从而降低TAE术后癌旁肝组织的氧化应激反应，进而对肝癌TAE术后癌旁肝组织具有保护作用。

Abstract: Objective: To explore the effect of Periplaneta americana extract on SOD and CAT in the liver tissue adjacent to the tumor after transcatheter arterial embolization (TAE) for liver cancer and its mechanism. Methods: In the preliminary observation, the liver function levels of 100 patients with primary liver cancer after TAE treatment were observed. Then, an animal experiment was conducted. Thirty-six male Japanese white rabbits with VX2 liver cancer models established by laparotomy tumor injection were randomly divided into 3 groups, with 12 rabbits in each group. The control group was the rabbit VX2 liver cancer model without any treatment; the TAE group was treated with iodized oil embolization of the tumor-feeding artery; the Periplaneta americana extract group was given 100 mg/kg of the extract daily from 3 days before the operation through the ear vein, with a dosage of 2 mL/kg once a day. The expression levels of PPAR-α and NF-κB in the liver tissue adjacent to the tumor in each group were detected by immunohistochemistry. The activities of SOD and CAT in the liver tissue adjacent to the tumor and the expression levels of NF-κB, SOD1, SOD2, and SOD3 mRNA were detected by bioenzymology in different experimental groups. Results: In the preliminary population study, the ALT levels before the operation, 3 days, 7 days, and 30 days after the operation were (83.89 ± 21.24), (63.59 ± 21.35), (57.89 ± 24.24) U/L, and the AST levels were (117.37 ± 27.40), (86.37 ± 27.53), (87.52 ± 30.40) U/L. Compared with before the operation, the ALT and AST levels 3 days, 7 days, and 30 days after TAE treatment were significantly increased (P < 0.05). The liver function indicators 7 days after the operation were significantly improved compared with 3 days after the operation. One month after the operation, there was no significant difference in the liver function indicators compared with before the operation (P > 0.05). The positive rates of PPAR-α in the control group, TAE group, and Periplaneta americana extract group were 4, 2, and 6, respectively, and the positive rates of NF-κB were 1, 9, and 2, respectively. Compared with the control group and the Periplaneta americana extract group, the positive rate of NF-κB and the level of NF-κB mRNA in the TAE group were significantly increased. Compared with the control group and the TAE group, the positive rate of PPAR-α and the level of PPAR-α mRNA in the Periplaneta americana extract group were significantly increased, and the differences were statistically significant (P < 0.05). The SOD levels in the control group, TAE group, and Periplaneta americana extract group after the operation were (22.48 ± 2.04), (21.81 ± 0.11), (25.81 ± 0.23) U/mgprot, and the CAT levels were (1.55 ± 0.19), (1.15 ± 0.25), (3.09 ± 0.57) U/mgprot. Compared with the control group and the Periplaneta americana extract group, the SOD and CAT levels in the TAE group were significantly decreased. Compared with the TAE group, the SOD and CAT levels in the Periplaneta americana extract group were significantly increased, and the differences were statistically significant (P < 0.05). Conclusion: Periplaneta americana extract can reduce the oxidative stress response in the liver tissue adjacent to the tumor after TAE for liver cancer by increasing the activities of antioxidant stress factors such as SOD and CAT, and thus has a protective effect on the liver tissue adjacent to the tumor after TAE for liver cancer.