替莫唑胺缓释微球治疗胶质瘤皮下移植瘤的实验研究

目的观察替莫唑胺缓释微球（P-TMZ）对SHG-44人脑胶质瘤皮下移植瘤的抑瘤效应。方法将SHG-44胶质瘤细胞（1×107）注射于Balb/c裸小鼠右腋皮下,再将皮下移植瘤以组织块接种的方法皮下传代（2mm3/鼠）。待肿瘤生长至约65mm3时,将荷瘤鼠随机分为瘤内注射替莫唑胺缓释微球（P-TMZ）组、替莫唑胺（TMZ）组、P-TMZ＋TMZ联合用药组、卡莫斯汀（BCNU）组、空白微球（P-0）组和生理盐水（NS）组,每组10只鼠。将P-TMZ（500mg/kg）和P-0（500mg/kg）以DMEM培养液混悬至终体积150μl,经皮多点穿刺缓慢注入肿瘤组织内;TMZ以50mg/kg灌胃,每日一次,连续5d;BCNU以40mg/kg尾静脉注射一次;NS以150μl瘤内注入。每4d测量荷瘤鼠肿瘤大小直至治疗后28d。结果 P-TMZ、P-TMZ＋TMZ和BCNU组抑瘤率均明显高于P-0、NS组（P〈0.01）,且抑瘤效应优于TMZ组（P〈0.05）;TMZ组抑瘤率高于P-0、NS组（P〈0.05）。结论 P-TMZ保留了TMZ的抑瘤活性,在局部应用时抑瘤效果优于TMZ。

Preliminaray Studies on Anti-glioma Effect of Temozolomide Delayed-Release Microspheres in Subcutaneous Xenograft Model

Objective To observe the anti-glioma effect of temozolomide delayed release microspheres P-TMZ in SHG-44 subcutaneous xenograft model. Methods The SHG-44 glioma cells（ 1 × 107） were inoculated subcutaneously into the right axil of Balb/c nude mice. The tumor was resected and cut into pieces,and inoculated subcutaneously （ 2 mm3 /mouse） . When xenograft tumor size reached about 65mm3,tumor-bearing mice were divided randomly into the 6 groups （ 10 mice/group） ,namely P-TMZ group,TMZ group,P-TMZ plus TMZ group ,BCNU group,the non-loaded microspheres （ P-0） group and normal saline （ NS） group. P-TMZ（ 500 mg/kg） ,and P-0（ 500 mg/kg） were suspended with DMEM to the final volume of 150μl and injected slowly into the tumors. TMZ（ 50 mg/kg） was administered with gavage everyday for 5 days. BCNU（ 40 mg/kg） was injected into the tail vein once,NS was injected directly （ 150 μl/mouse） into tumor tissues. Tumor size was measured every 4 days till 28 days after treatment. Results Tumor inhibition ratios of P-TMZ,P-TMZ plus TMZ ,and BCNU were significantly higer than P-0 and NS（ P 0. 01） ; P-TMZ,P-TMZ plus TMZ and BCNU were more effective than TMZ （ P 0. 05） . TMZ showed definite anti-tumor effect when compared with P-0,NS （ P 0. 05） . Conclusion P-TMZ retaines anti-tumor activity of TMZ and has better therapeutic effect against glioma when administered locally.