摘要： 目的 利用兔VX2肝癌模型探讨喜树碱在肝动脉化疗栓塞术中的作用及其机制。方法 将兔VX2瘤株种植于肝脏内建立兔VX2肝癌模型, 并对其进行肝动脉化疗栓塞术。实验分为单纯栓塞组(仅进行肝动脉栓塞, 不使用化疗药物,A组)、栓塞联合喜树碱组[肝动脉栓塞同时灌注喜树碱(2 mg/kg), B组]、栓塞联合阿霉素组[肝动脉栓塞同时灌注阿霉素(1 mg/kg), C组]、栓塞联合喜树碱与阿霉素组[肝动脉栓塞同时灌注喜树碱(2 mg/kg)、阿霉素(1 mg/kg), D组] 4组, 每组6只。分别于手术前1 d, 手术后3、7 d检测各组谷丙转氨酶(ALT)、谷草转氨酶(AST) 水平; 手术前1 d及手术后7 d核磁共振检查肿瘤体积并计算肿瘤生长率; 免疫组化染色检测各组NRF2、ki-67的表达情况。比较各组肝功能指标、肿瘤生长率、肿瘤病理结果以及NRF2、Ki-67的表达。结果 与术前比较, A组术后ALT、AST水平未出现明显升高(P > 0.05), 而B、C、D组术后3 d、7 d ALT、AST水平明显升高(均P < 0.05)。与A组比较,C组、D组肿瘤生长率均降低(均P < 0.01); 而D组降低更显著(P < 0.001)。与A组比较,B、C、D组Ki-67表达均降低(P < 0.01), 其中D组降低最显著(P < 0.001)。与A组比较, B组、D组NRF2表达均明显下降(P < 0.001)。结论 喜树碱可明显提高兔VX2肝癌肝动脉化疗栓塞术的治疗效果, 其作用可能是通过抑制NRF2表达来实现的。

喜树碱在肝动脉化疗栓塞术中的作用及其机制

王鑫磊, 冯博

中国医科大学附属第一医院介入治疗科, 沈阳 110001

收稿日期:2021-12-18出版日期:2022-08-30发布日期:2022-07-19
通讯作者:冯博E-mail:fbcmu@sina.com
作者简介:王鑫磊（1993-），男，医师，硕士.
基金资助:辽宁省教育厅地方服务项目（LFWK201704）


关键词: 喜树碱, 兔VX2肝癌模型, 肝动脉化疗栓塞术
Abstract: Objective To investigate the effect and mechanism of camptothecin on hepatic arterial chemoembolization in a VX2 hepatic carcinoma model. Methods Rabbit VX2 tumor strain was implanted into the liver to establish the rabbit VX2 hepatocellular carcinoma model, after which hepatic artery chemoembolization was performed. The experiment was divided into four groups:group A(hepatic artery embolization only, without chemotherapy drugs), group B[hepatic artery embolization with camptothecin(2 mg/kg)], group C[hepatic artery embolization with doxorubicin(1 mg/kg)], and group D[hepatic artery embolization with doxorubicin(1 mg/kg) and camptothecin(2 mg/kg)]. Each group consisted of six rabbits. Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were detected 1 day preoperatively, 3 and 7 days after surgery, respectively. Tumor volume and tumor growth rate were measured using MRI 1 day preoperatively and 7 days postoperatively. The expression of NRF2 and KI-67 was detected using immunohistochemical staining. Liver function index, tumor growth rate, tumor pathology, and NRF2 and KI-67 expression were compared among all groups. Results Compared to the levels 1 day preoperatively, the levels of ALT and AST in group A were not significantly increased postoperatively(P > 0.05), while the levels of ALT and AST in groups B, C and D were significantly increased 3 days, 7 days postoperatively(all P < 0.05). Compared to group A, the tumor growth rates in group C and group D were decreased(both P < 0.01). The decrease was more significant in group D(P < 0.001). Compared to group A, the expression of Ki-67 in groups B, C, and D was also decreased(all P < 0.01), and group D had the most significant decrease(P < 0.001). Compared to group A, NRF2 expression in group B and D decreased significantly(both P < 0.001). Conclusion Camptothecin can significantly improve the therapeutic effect of hepatic arterial chemoembolization for VX2 carcinoma in rabbits, which may be achieved by inhibiting NRF2 expression.
Key words: camptothecin, rabbit VX2 hepatoma model, hepatic arterial chemoembolization
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