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载阿霉素纳米金联合肝动脉栓塞及光热消融治疗兔VX-2肝癌的实验研究

发布时间:2018-10-18 10:10
【摘要】:目的:研究同时经肝动脉灌注载阿霉素纳米金(doxorubicin-loaded gold nanoparticles,Dox-AuNPs)和利用碘化油行肝动脉栓塞术后,联合近红外光照射行光热消融治疗兔VX-2肝癌的有效性和安全性。材料与方法:40只新西兰大白兔随机分为5组,每组8只,分别为载阿霉素纳米金-碘油栓塞联合光热消融组(A组),载阿霉素纳米金-碘油栓塞组(B组),碘油-阿霉素混悬液栓塞组(C组),单纯碘油栓塞组(D组)和生理盐水组(E组)。建立兔VX-2移植性肝癌模型,于建模后2周分别利用不同实验组药物及方法行介入治疗。分别于介入治疗当日,介入术后3天、7天、14天行肝脏增强CT检查,评估肿瘤体积变化;于介入治疗当日,介入术后3天、7天、14天抽血化验肝肾功,评估肝肾功能变化。每组8只兔,随机选择4只于介入治疗后14天处死,观察大体标本特点,取肿瘤组织行病理及免疫组化检查;每组另4只兔饲养至死亡,统计比较各组术后总生存期。结果:各组术前基线值无明显统计学差异(P0.05)。所有动物均成功进行介入治疗且存活至术后14天,均未出现严重并发症。A~E五组实验兔术前肿瘤体积分别为1.38±0.71、1.27±0.62、1.52±0.86、1.45±1.04、1.35±0.48cm3;术后 3 天肿瘤体积分别为 1.35±0.69、1.30±1.02、1.48±1.21、1.50±0.86、1.40±0.76 cm3;术后 7 天肿瘤体积分别为 1.44±0.72、2.85±2.03、6.79±2.87、6.18±3.21、7.38±3.36cm3;术后 14 天肿瘤体积分别为 3.01±1.89、4.34±2.32、8.86±3.49、9.02±4.38、18.7±10.7cm3,术后 7、14 天组间比较有统计学差异(P0.05)。A~E 组术后生存期分别为 25.3±3.1、21.5±3.4、20.3±4.7、20.5±3.4、17.0±2.7 天,组间比较有统计学差异(P0.05)。A~E组病理显示镜下肿瘤细胞坏死率分别为(%)3.55±1.11、2.04±1.76、1.76±1.70、1.60±0.92、0.27±0.29,组间比较有统计学差异(P0.05)。A~E组免疫组化显示镜下肿瘤内微血管密度分别为1.8±0.7、3.2±1.3、3.9±1.2、3.8±1.6、2.5±1.0条,组间比较有统计学差异(P0.05);镜下VEGF积分光密度值分别为:2942.1±649.3、5686.4±2393.1、8364.7±3979.1、7523.6±3584.6、20597.8±9058.0,组间比较有统计学差异(P0.05)。A组同B、C、D三组比较,ALT、AST值在术后3、7、14天均无明显统计学差异(P0.05),同E组比较,ALT、AST值在术后3、7、14天均有明显统计学差异(P0.05);各组术前,术后3、7、14天CREA、UREA值均无明显统计学差异(P0.05)。结论:本研究通过对比研究载阿霉素纳米金、肝动脉栓塞、光热消融三者联合与载阿霉素纳米金、肝动脉栓塞两者联合及传统肝动脉化疗栓塞等不同方法治疗兔VX-2肝癌的疗效及安全性,表明载阿霉素纳米金、肝动脉栓塞、光热消融三者联合可提高兔VX-2肝癌的治疗效果,且未额外增加肝肾毒性,较为安全。
[Abstract]:Objective: to study the efficacy and safety of simultaneous transarterial infusion of doxorubicin nanogold (doxorubicin-loaded gold nanoparticles,Dox-AuNPs) and lipiodol for hepatic artery embolization combined with near-infrared irradiation in the treatment of rabbit VX-2 liver cancer. Materials and methods: forty New Zealand rabbits were randomly divided into 5 groups with 8 rabbits in each group. Doxorubicin nano-gold-lipiodol embolization combined with photothermal ablation group (group A), doxorubicin nano-gold-lipiodol embolization group (group B), lipiodo-doxorubicin suspension embolization group (group C), simple lipiodol embolization group (group D) and saline group (group E). The VX-2 transplanted liver cancer model was established in rabbits. Two weeks after modeling, different drugs and methods were used for interventional therapy in different experimental groups. On the day of interventional therapy, 3 days, 7 days and 14 days after interventional therapy, liver enhanced CT was performed to evaluate the changes of tumor volume, and on the day of interventional therapy, 3, 7 and 14 days after interventional therapy, blood samples were taken to test liver and kidney function to evaluate the changes of liver and kidney function. Eight rabbits in each group were randomly selected to be killed 14 days after interventional therapy, the characteristics of gross specimens were observed, and the tumor tissues were taken for pathological and immunohistochemical examination, and 4 rabbits in each group were raised to death, and the total survival time of each group was compared statistically. Results: there was no significant difference in preoperative baseline value in each group (P0.05). All animals were successfully treated with interventional therapy and survived until 14 days after operation. 鍧囨湭鍑虹幇涓ラ噸骞跺彂鐥,

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