姜黄素对N-甲基亚硝基脲诱发膀胱癌大鼠化学干预作用及机制分析  

Effect of curcumin on chemical intervention and mechanism of MNU-induced bladder cancer in rats

作　　者：吴金生 王清明 郑传秋 纪萌[2] 孙立江[1] 

机构地区：[1]青岛大学,山东青岛市266071 [2]潍坊医学院,山东潍坊市261053

出　　处：《中国实验动物学报》2017年第5期567-571,共5页Acta Laboratorium Animalis Scientia Sinica

摘　　要：目的分析姜黄素对N-甲基亚硝基脲（MNU）诱导的膀胱癌大鼠模型的化学干预作用及作用机制。方法将100只SD大鼠随机分为四组,对照组（10只）、模型组（10只）、干预组（40只）和治疗组（40只）,对照组等时等量的膀胱灌注生理盐水,其他三组均对大鼠进行膀胱灌注MNU,诱发SD大鼠形成膀胱癌模型（将浓度为1 mg/m L的MNU溶液灌注入膀胱内,MNU灌注时间为第2、4、6和8周,每次2 mg,每2周1次,共4次）,模型组在诱发大鼠膀胱癌时膀胱灌注蒸馏水,干预组在膀胱灌注MNU时灌注姜黄素溶液（400μmol/L）,即第1、3、5、7和9周膀胱灌注,第10周安乐死大鼠;治疗组在诱发大鼠膀胱癌模型后膀胱灌注姜黄素溶液（400μmol/L）,即在第10、12、14、16、18周时间内持续膀胱灌注,在第19周时处死大鼠,获得的膀胱组织依次通过苏木精-伊红（HE）染色,观察病理变化;TUNEL末端标记法测定肿瘤组织中细胞凋亡情况;Western blot检测凋亡相关蛋白表达。结果模型组在第10周时膀胱癌的发生率为90%（9/10）,干预组在第10周时大鼠膀胱癌的发生率为12.5%（5/40）,治疗组第10周时膀胱癌的发生率为92.5%（37/40）,比较干预组与模型组大鼠膀胱癌的发生率差异有显著性（P〈0.05）,说明姜黄素对MUN诱发膀胱癌大鼠有明显的化学干预作用;在治疗组膀胱癌形成后给予姜黄素治疗,第19周膀胱癌发生率为78.4%（30/37）,与治疗前的第10周比较说明姜黄素对膀胱癌有治疗作用,可以延缓膀胱癌的恶化。TUNEL实验证实姜黄素显著促进膀胱癌细胞的凋亡,抑制膀胱癌细胞的增殖。Western blot结果发现,姜黄素抑制NF-κB的激活,有效下调NF-κB调节的基因产物的表达。结论姜黄素对MNU诱导的膀胱癌大鼠模型有明显的的化学干预作用,且作用机制可能是通过抑制NF-κB的激活并且有效下调NF-κB调节的基因产物,来调节膀胱癌中相关蛋白的表�Objective To study the effect of curcumin on rat model of N-methylnitrosourea（ MNU）-induced bladder cancer and its mechanism. Methods One hundred SD rats were randomly divided into four groups： control group（ n = 10）,model group（ n = 10）,intervention group（ n = 40） and treatment group（ n = 40）. Rats in the control group received intravesical infusion of distilled water. Rats in the other three groups were given MNU（ 1 mg/m L） in 2 m L saline at2 nd,4th,6th and 8th weeks to induce bladder cancer. In the model group,the rats were injected with distilled water in the bladder. The rats in the intervention group received 2 m L curcumin solution（ 400 μmol/L） at the 1st,3rd,5th,7th and 9th weeks,and were sacrificed at the 11 th week. In the model group,the rats were injected with distilled water in the bladder. In the treatment group,the rats had intravesical instillation of curcumin in the bladder（ 400 μmol/L,2 m L） at10,12,14,16,and 18 weeks,and sacrificed at the 19 th week. Bladder tissue samples were taken for pathological examination using hematoxylin and eosin（ HE） staining. TUNEL staining assay was used to detect the apoptosis in tumor tissue.The expression of apoptosis-related proteins was detected by Western blot. Results The incidence of bladder cancer was90%（ 9/10） in the model group,12. 5%（ 5/40） in the intervention group and 92. 5%（ 37/40） in the treatment group at the 10 th week,showing a significant difference between the intervention group and model group（ P〈0. 05）,indicating an obvious interventional effect of curcumin on the bladder cancer. The incidence rate of bladder cancer in the treatment group was 78. 4%（ 30/37） at the 19 th week,and compared with the 10 th week before treatment,showing that curcumin can delay the recurrence of bladder cancer. TUNEL staining assay confirmed that curcumin significantly promoted the apoptosis in bladder cancer cells and inhibited their proliferation. The Western blot analysis showed that curcumin inhibit

关 键 词：姜黄素 N-甲基亚硝基脲 膀胱癌 化学干预 作用机制 大鼠 

分 类 号：Q95-33[生物学—动物学]