介入导人三氧化二砷微球对VX2兔肝肿瘤模型的治疗作用

The treatment effect of As_2O_3-PLGA microspheres on VX2 rabbits liver tumor models

目的观察介入导入三氧化二砷(As_2O_3)微球对VX2兔肝肿瘤模型的治疗作用。方法新西兰大白兔32只,体重2．3～2．8 kg,制作VX2兔肝肿瘤模型并随机分成4组,每组8只,均经右侧股动脉插管至肝动脉,向肿瘤供血动脉给药:a组动脉灌注组:As_2O_3 3 mg/kg+生理盐水10 ml;b组As_2O_3微球栓塞组:注入As_2O_3 PLGA微球3 mg/kg;c组空白微球栓塞组:注入PLGA微球3 mg/kg;d组为对照组:经肝动脉注入生理盐水10 ml。兔肝肿瘤模型制作后14 d行肝螺旋CT双期动态扫描,根据螺旋CT扫描获得肝内肿瘤影像,测量肿瘤大小,次日行介入治疗,术后第21天处死实验兔后,取出肝脏,测量瘤体大小;肿瘤组织4%甲醛固定,多点取材,HE染色,显微镜检。结果实验兔介入操作均获成功,且均存活。肿瘤平扫呈低密度,与周围正常肝实质分界欠清。增强后动脉期肿瘤强化明显,坏死组织无强化,呈不均匀高密度,肿瘤与周围肝实质分界清楚。门脉期肿瘤呈不均匀低密度,而周围正常肝实质强化明显,术后CT随访d组和a组肿瘤明显增大,中央呈低密度;c组肿瘤有轻度强化,b组肿瘤体积小,呈低密度,边界清楚,强化不明显。各组肿瘤体积术前无统计学差异,术后标本体积测量显示As_2O_3微球栓塞组瘤体最小,a、b、c组与d组间有显著统计学差异(P＜0．05);b组与c组、a组间有显著统计学差异(P＜0．05)。病理检查显示a组和d组肿瘤体积大,呈鱼肉样,质地脆,坏死区位于肿瘤中心区域,白色豆渣样,肿瘤血管丰富;显微镜下肿瘤细胞丰富,巢团状排列,纤维样组织少与正常肝组织分界不清,呈浸润性生长。b组肿瘤体积小,坏死明显,坏死区边缘纤维组织丰富,在纤维组织内可见残存瘤巢。在纤维组织外围见到肝细胞空泡变性,呈片状分布。结论As_2O_3 PLGA微球对VX2兔肝肿瘤有良好的化疗栓塞效果,使用安全。

Objective To assess the treatment effects of As2O3-PLGA mierospheres on VX2 rabbits liver tumor models. Methods Thirty-two New Zealand white rabbits were involved with formation of VX2 rabbits liver tumor models, and randomly divided into 4 groups of 8 each.（a） As2O3. plus 0.9% NaCl solution group： 3 F co-catheter was plugged into hepatic artery, and then As2O3 （3 mg/kg）plus 10 ml 0.9%NaCl solution was injected into the tumor through the feeding artery; （b）As2O3 PLGA microspheres group：As2O3- PLGA microspheres （3 mg/kg） was injected into the tumor through the feeding artery; （c）PLGA microspheres group： Injection of PLGA microspheres （3 mg/kg）injected into the tumor through the feeding artery; （d） control group： 0.9% NaCl solution（10 ml） was injected into the feeding artery. Dual phase helical CT scans were performed the day before treatment, 20 days after treatment and finally the rabbits were sacrificed. The sizes of the tumor were measured and followed by histopathological analysis and HE staining. Results The volumes of tumors post operatively of group a, b, c and d were （31.08 ± 11.15） cm^3, （3.82 ± 2.537） cm^3, （13.22 ± 4.665） cm^3 and （115.8 ± 62.01） cm^3 respectively. The most significant treatment effect was available in group b, with more coagulation necrosis and fibrofic tissue formation. Statistical analysis indicated that the treatment effects of group a, b, c were better than that of group d with significant difference which can be also seen between group a and b, group b and c. Conclusion As2O3-PLGA microspheres shows rather excellent chemoembolization effects on VX2 rabbit liver tumor model with safely.