青蒿琥酯聚乳酸微球栓塞治疗兔VX2移植性肝癌的研究

Study of Artesunate Polylactic Acid Microspheres with Chemoembolization on Hepatic Tumor of Rabbit VX2

关键词:  青蒿琥酯  聚乳酸微球  经动脉化疗栓塞  VX2肝癌

Key words:  artesunate  polylactic acid microspheres  transarteria chemoembolization  VX2 tumor

摘要:

目的 研究青蒿琥酯聚乳酸微球栓塞治疗兔VX2移植性肝癌的疗效。方法 将VX2瘤粒直接种植于新西兰大白兔左肝内2周，CT证实已成功接种VX2的荷瘤兔随机分为4组，每组10只，经股动脉微导管超选择性肝动脉插管分别给予不同处理：青蒿琥酯聚乳酸微球(ART-PLA-MS)组，注入ART-PLA-MS 76.0 mg·kg^-1；青蒿琥酯(artesunate，ART)溶液组，注入ART溶液23.4 mg·kg^-1；空白微球组，注入空白聚乳酸微球52.6 mg·kg^-1；空白对照组，注入2 mL复方泛影葡胺溶液。每天观察动物生长情况，术后2周处死动物，测量肿瘤体积、坏死区面积，计算肿瘤生长率、坏死率；实验兔于治疗前及治疗后第1，3，7天经耳缘静脉采血，检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)及肌酐(Cr)值，评价肝肾功能情况。结果 术前1 d 4组动物肿瘤体积差异无统计学意义。治疗后2周，与其他3组比较，ART-PLA-MS组肿瘤体积、肿瘤生长率和肿瘤坏死率差异均具有统计学意义(P<0.01)；与空白对照组比较，空白微球组肿瘤体积和坏死率差异有显著统计学意义(P<0.01)，肿瘤生长率有统计学意义(P<0.05)；与ALT溶液组比较，空白微球组肿瘤坏死率差异有显著统计学意义(P<0.01)，肿瘤体积和生长率有统计学意义(P<0.05)；与空白对照组比较，ALT溶液组差异无统计学意义。治疗前，4组ALT、AST、BUN及Cr值值无统计学差异；治疗后1，3 d，ART-PLA-MS组、ALT溶液组和空白微球组ALT、AST、BUN及Cr值均显著升高(P<0.05)；治疗后7 d，各组肝肾功能均恢复至治疗前水平。结论 ART-PLA-MS经肝动脉栓塞对兔VX2肝癌具有一定的治疗作用。

Abstract:

OBJECTIVE To investigate the therapeutic effect of artesunate polylactic acid microspheres(ART-PLA-MS) with chemoembolization on hepatic tumor of rabbit VX2. METHODS VX2 tumor pieces were surgically implanted into the left liver lobe of New Zealand white rabbits. Two weeks later, 40 rabbits with experimental hepatic tumors diagnosed by CT were randomly divided into 4 groups with 10 rabbits in each group. All rabbits were dealed with superselective hepatic arterial catheterization with micro-catheter technique via femoral artery. The rabbits in ART-PLA-MS group were infused with 76.0 mg·kg^-1 ART-PLA-MS. In ART solution group, the rabbits were infused with 23.4 mg·kg^-1 ART solution. In blank MS group, the rabbits were given 52.6 mg·kg^-1 blank MS. In control group, the rabbits were given 2 ml Compound Diatrzoatc Meglumlne. The common conditions of the rabbits were observed daily after operation. Two weeks after treatment, all the experimental rabbits were sacrificed and the volume and necrotic area of the implanted tumor were measured. Blood of all the experimental rabbits were got before and the first, third and seventh day after the treatment for detection of ALT, AST, BUN and Cr. RESULTS There were no significant difference in tumors’ volume among 4 groups at 1 day before operation. Two weeks after treatment, compared with other 3 groups, the average volume, the growth rate and necrotic rate of the implanted tumors in ART-PLA-MS group were significantly different(P<0.01). The average volume, necrotic rate of the implanted tumor were significantly different between blank MS group and control group(P<0.01), and the growth rate was different between this two groups(P<0.05). Between blank MS group and ART solution group, the necrotic rate of the implanted tumor was significantly different(P<0.01), the average volume and the growth rate were different(P<0.05), while there was no significant difference in ART solution group and control group. There were no significant difference in ALT, AST, BUN and Cr among 4 groups before operation. ALT, AST, BUN and Cr were significantly increased in the first and third day in ART-PLA-MS group, ART solution group and blank MS group after operation(P<0.05), and recovered in the seventh day. CONCLUSION The artesunate polylactic acid microspheres with chemoembolization has significant therapeutic effect on hepatic tumor of rabbit VX2.