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目的研究载阿霉素液-固相变型原位凝胶(DOX凝胶)治疗高强度聚焦超声(HIFU)消融兔VX_2肿瘤后残余瘤的作用。方法制备DOX凝胶,高效液相色谱法测定其体外释药率。建立兔VX_2皮下移植瘤模型,HIFU不全消融后瘤内注射DOX凝胶进行治疗。对空白组、对照组(HIFU+无药凝胶)及治疗组(HIFU+DOX凝胶)治疗4、8 d后,测量肿瘤体积,观察HE染色,免疫组化和TUNEL法检测肿瘤细胞增殖和凋亡。结果 DOX凝胶体外累积释药率为(78.92±4.68)%。治疗后,治疗组肿瘤体积较其他组小(P<0.05),HE染色可见消融坏死区及少量肿瘤细胞,细胞增殖指数较其他组低(P<0.05),而凋亡指数较高(P<0.05)。结论 DOX凝胶能有效治疗HIFU消融后的残余瘤,有望成为HIFU消融肿瘤后残余瘤的治疗及预防复发的新手段。
Objective To investigate the effect of doxorubicin-solid phase in situ gels (DOX gel) on residual tumor after laser ablation of rabbit VX_2 tumor by high intensity focused ultrasound (HIFU). Methods DOX gel was prepared and its in vitro drug release rate was determined by high performance liquid chromatography. Rabbit VX_2 subcutaneously transplanted tumor model was established, and after intratumoral injection of DOX gel for incomplete HIFU ablation. After treatment for 4 and 8 days, the tumor volume was measured in the blank group, the control group (HIFU + non-drug gel) and the treatment group (HIFU + DOX gel), and HE staining was used to observe the proliferation and apoptosis of tumor cells by immunohistochemistry and TUNEL Death. Results The cumulative drug release rate of DOX gel in vitro was (78.92 ± 4.68)%. After treatment, the tumor volume in the treatment group was smaller than that in other groups (P <0.05). The area of ablation necrosis and a few tumor cells were observed by HE staining. The cell proliferation index was lower (P <0.05) and the apoptosis index was higher (P < 0.05). Conclusion DOX gel can effectively treat the residual tumor after HIFU ablation, which is expected to be a new treatment for residual tumor after HIFU ablation and a new way to prevent relapse.