载5-氟尿嘧啶纳米微球治疗荷H22腹水瘤小鼠的实验研究

Experimental study on 5-FU loaded nanoparticles in the treatment of H22-bearing ascites tumor mice

目的观察自制载5-氟尿嘧啶(5-FU)纳米微粒对荷H22小鼠恶性腹水的治疗作用以及对小鼠生存期、小鼠体重、H22细胞周期、小鼠肝脏毒性的影响。方法 168只荷H22腹水瘤昆明小鼠随机分为7组,即空白对照组、溶剂对照组、辅料对照组、5-FU阳性药组(5d共3mg),低(5d共0.12mg)、中(5d共0.6mg)、高(5d共3mg)剂量微粒缓释组。药物经腹腔注入,微粒缓释组只给药一次,其他组均为连续给药5d,每天一次。观察各组小鼠生存情况,比较各组小鼠平均生存时间、小鼠体重、细胞增殖指数(PI)以及肝脏毒性。结果与对照组比较,微粒缓释组能明显提高小鼠的生存时间(P<0.05)、减小小鼠体重(P<0.05)和增殖指数(PI)、减小肝毒性。与阳性药物组比较,中、高剂量微粒缓释组对小鼠H22腹水瘤的抑制作用增加,表现为明显延长生存时间(P<0.05)、减缓小鼠体重增长(P<0.05)和减小增殖指数(PI),药物对肝脏毒性影响也有减小,表现为中剂量组肝脏毒性明显降低,高剂量组肝脏毒性与阳性药物组相当。结论 5-FU载药缓释纳米微球在治疗荷H22腹水瘤小鼠时可以在小鼠体内持续释放,与阳性药物组相比减少了给药次数,增加了药物对H22肿瘤细胞的抑制作用,并减小对肝脏的毒性。

Objective To observe the effect of 5-FU loaded nanoparticles in treatment of H22-bearing ascites tumor mice.The survival time,the body weight growth,cell cycle of H22 cell and liver histological were examined.Methods 168 Kunming mice of ascites tumor model were made by inoculated with tumor cells（H22）,and randomly divided into the control group,solvent group,placebo group,5-FU group（3 mg in 5 days）,low（0.12 mg in 5 days）,middle（0.6 mg in 5 days）,high（3 mg in 5 days）dose 5-FU loaded nanoparticles groups.5-FU loaded nanoparticles groups were given a does for 5 days,all other group were given a does for one day averagely.The anti-tumor activity was evaluated by life prolonging rate,body weight growth,and PI index of cell cycle.And the drug toxicology was measured by liver histological examination.Results Compare with the control group,the anti-tumor activity of middle and high concentration 5-FU loaded nanoparticles groups were significantly increased.Compare with 5-FU drug group,the life prolonging rate was significantly increased（P0.05）,and body weight growth,PI index of cell cycle in the middle and high concentration 5-FU loaded nanoparticles groups were significantly decreased（P0.05）.Liver histological examination showed the drug toxicology in the middle concentration 5-FU loaded nanoparticles group was much smaller than 5-FU drug group which was approximative high concentration 5-FU loaded nanoparticles group.Conclusions Because of the sustained release nanoparticles could keep drug concentration,5-FU loaded nanoparticles increased the anti-tumor activity and decreased the drug toxicology in the treatment of H22-bearing ascites tumor mice.