塞来昔布联合卡介苗治疗大鼠膀胱肿瘤的实验研究

Effect of BCG combined with celecoxib on the animal model of bladder tumor

目的:观察联合应用塞来昔布与卡介苗治疗大鼠膀胱肿瘤的疗效,并探讨其机制。方法:选用5～6周龄雌性Wistar大白鼠40只,随机分为4组,即PBS组、塞来昔布组、卡介苗组、塞来昔布+卡介苗组。均采用膀胱灌注MNU(N-甲基亚硝基脲)制成大鼠膀胱肿瘤模型,于灌注MNU后第10周开始给予相应的药物干预治疗,于第13周处死所有大鼠,观察膀胱肿瘤的形成情况,免疫组织化学检测肿瘤组织中的CD3+、CD4+、CD8+细胞的浸润情况,TUNEL法检测肿瘤细胞的凋亡指数(apoptotic index,AI)。结果:联合用药组CD3+、CD4+、CD8+细胞浸润百分比及肿瘤细胞AI值与其他组相比,差异有统计学意义(P<0.05)。结论:联合应用塞来昔布和卡介苗比单纯使用卡介苗或塞来昔布能更加明显地抑制大鼠膀胱肿瘤的生长,其机制可能是通过促进免疫系统的功能和诱导肿瘤细胞凋亡增加而发挥作用的。

Objective： To observe the effect of Celecoxib combined with BCG on the Wistar rats model of bladder tumor and discuss the mechanism of the therapeusis. Methods： Separated forty female 5-6 week-old Wistar rats into four groups： PBS groups, Celecoxib groups, BCG groups, Celecoxib＋ BCG groups randomly. All the rats were irrigated MNU（M-methyl- N-nitrosourea） into their bladders to make of the bladder tumor models. Treatment took place on tenth week after irrigated MNU, four groups were irrigated corresponding drug into bladders; at thirteen week executed all rats, observed the development of bladder tumor, detected infiltrating condition of CD3^＋, CD4^＋, CD8^＋ cells in tumor tissues with immunohistochemistry, detected apoptosis condition of tumor cells with the method of TUNEL. Results： Celecoxib＋ BCG groups compared with the other groups,the difference of the infiltration percentage of CD3^＋, CD4^＋, CD8^＋ cell and the degree of tumor cell apoptosis has statistical significance （P〈0.05）. Conclusion： Combined Celecoxib and BCG can be more conspicuous inhibition of tumor growth of rat bladder than the use of celecoxib or BCG alone, The mechanism is maybe that promoting the function of immune system and increasing tumor cells apoptosis.