吡柔比星联合干扰素抑制大鼠膀胱癌生长的机制

The Suppression Mechanism of the Growth of Bladder Cancer on Pirarubicin Combined with Interferon

目的探讨吡柔比星联合干扰素α-2b膀胱灌注对大鼠膀胱肿瘤生长的抑制作用和机制。方法 80只雌性Wistar大鼠随机分为对照组、吡柔比星组、干扰素组和联合用药组,每组20只。制作N-甲基亚硝基脲诱导大鼠原位膀胱癌模型,于第8周分别以生理盐水、吡柔比星、重组干扰素α-2b和吡柔比星+重组干扰素α-2b连续膀胱灌注,每周1次,共6次。第8和14周进行病理观察,第14周测量膀胱质量,免疫组织化学法检测微血管密度(MVD),流式细胞仪测凋亡指数(AI)。结果第8周时,各组大鼠膀胱黏膜呈不典型增生和移行细胞癌Ⅰ级。第14周时,可见菜花状、多发膀胱肿瘤并侵入肌层。吡柔比星组和联合用药组大鼠膀胱质量小于对照组(P<0.01),联合用药组大鼠膀胱质量小于吡柔比星组(P<0.05),联合用药组MVD小于干扰素组(P<0.01),联合用药组大鼠的AI高于其他3组(P<0.01),吡柔比星组和干扰素组的AI大于对照组(P分别<0.01和0.05)。结论吡柔比星联合干扰素α-2b膀胱灌注可抑制大鼠膀胱肿瘤生长,其机制与二者协同作用抑制肿瘤血管生长和诱导肿瘤细胞凋亡有关。

Objective To observe the suppression mechanism of the growth of bladder cancer on pirarubicin combined with interferon.Methods 80 female Wistar rats were randomly divided into four groups：control group,pirarubicin group,interferon group and combination group.Establish N-nitrosourea Induction model of rat orthotopic bladder cancer,four groups were respectively received a total of six times（every week） intravesical instillation of physiologic saline,pirarubicin,interferon（α-2b） and combination drugs from the eighth week,Pathological observation was done at the 8th week and the 14th week.The weights of bladders,microvessel densities（MVD） and apoptotic indexes（AI） were investigated.Results The mucosal of bladder was showed dysplasia and transitional cell I in both groups at the 8th week.Muscle layer of bladder could be seen cauliflower-like,multiple bladder tumors at the 14th week.The weight of bladder in pirarubicin group and combination group were less than those of control group（P 0.01）,the latter was less than that of pirarubicin group（P 0.05）.The MVD of combination group was less than that of interferon group（P 0.01）,and the AI of it was higher than that of other three groups（P 0.01）.The AI of pirarubicin group and interferon group were higher than those of control group（P 0.01,P 0.05）.Conclusion Intravesical instillation of pirarubicin and interferon could inhibit the growth of bladder tumour by restraining angiogenesis and accelerating apoptosis in rats.