华蟾素对SD大鼠膀胱肿瘤的抑制作用

Therapeutic effect of cinobufagin on bladder tumor in SD rats:an in vivo experiment

目的研究华蟾素对SD大鼠膀胱肿瘤的治疗作用。方法 50只SD大鼠按随机分为对照组和实验组,实验组40只大鼠膀胱灌注N-甲基-N-亚硝基脲(N-methyl-N-nitrosourea,MUN),每3周1次,共4次;于第14周将实验组大鼠随机分为生理盐水组(膀胱灌注生理盐水)、丝裂霉素组(5 mg/kg)、低浓度华蟾素组(5 mg/kg)及高浓度华蟾素组(20 mg/kg),每周灌注1次,连续灌注5次,计算抑瘤率,TUNEL法检测肿瘤细胞的凋亡情况。结果 MNU膀胱灌注成功建立膀胱肿瘤动物模型,以膀胱肿瘤质量计算高浓度华蟾素组的抑瘤率为76.7%,高浓度华蟾素组抑瘤率较丝裂霉素组及低浓度华蟾素组高;TUNEL法检测高浓度华蟾素组AI值为(24.21±1.24)%,较其他各组AI值明显增高,提示高浓度华蟾素组凋亡指数高于丝裂霉素及低浓度华蟾素组。结论华蟾素对膀胱肿瘤有抑制生长、促进凋亡的作用,且高浓度时抑瘤作用及促凋亡作用较强。

Objective To study the therapeutic effect of cinobufagin on bladder cancer. Methods Fifty SD rats were randomly divided into experimental group （n = 40） and control group （n = 10）. N-methyl-N- nitrosourea （N-MNU） was infused into bladder of rats in experimental group （2.5 mg every 3 weeks, for 4 times）, and after that, the rats of later group were divided into saline group, mitomycin group （5 mg/kg）, low dose cinobufagin group （5 mg/kg） and high dose cinobufagin group （20 mg/kg）, into which saline, mitomycin, low and and high dose cinobufagin were infused, once a week, for 5 times. Tumorinhibiting rate of cinobufacin was calculated and apoptosis of tumor cells was detected by TUNEL assay. Results The animal bladder tumor model was successfully established by infusing N-MNU into bladder. The tumor-inhibiting rate was 76.7% and the apoptosis index （AI） was （24.21 ＋ 1.24）% in high dose cinobufotalin group, which were significantly higher than those in low dose cinobufotalin group and mitomycin group （ P 〈 0. 05）. Conclusion Cinobufagin can inhibit the growth of bladder tumor in SD rats, and promote apoptosis of bladder tumor cells. The higher the cinobufotalin level is, the stronger the apoptosis-promoting effect of cinobufotalin is.