姜黄素对马兜铃酸诱发的膀胱肿瘤的预防作用

Preventive Effects of Curcumin in Rat Bladder Tumor Induced by Aristolochic Acid

目的以马兜铃酸诱发的膀胱癌为模型,观察姜黄素对膀胱组织的病理变化、Ras蛋白和p53蛋白及细胞角质蛋白20(CK20)的变化,评价姜黄素对马兜铃酸诱导膀胱癌的化学预防作用及发生机制。方法50只大鼠随机分为对照组、诱癌组、预防组三组。诱癌组:给予10mg(kg·d)马兜铃酸给大鼠灌胃,连续诱癌3个月;预防组:在诱癌的同时给予含2%姜黄素粉的饲料进行化学防护;对照组:为正常饮食和饮水。3个月后宰杀全部大鼠,取膀胱组织进行HE染色显微镜下观察病理变化,用免疫组化染色技术检测膀胱组织内Ras、p53蛋白的变化,荧光定量PCR技术检測CK20 mRNA。结果经3个月诱癌,膀胱癌的发生率在诱癌组为95%(19/20),而姜黄素预防组,膀胱癌的发生率仅为10%(2/20),对照组膀胱黏膜组织Ras、p53蛋白及CK20 mRNA均呈阴性表达,预防组及诱癌组膀胱黏膜组织Ras、p53蛋白及CK20 mRNA均呈阳性,且以诱癌组更明显,差异具有统计学意义(P<0.001)。结论姜黄素对马兜铃酸诱导的膀胱癌具有良好的化学预防作用,可能分子机制与抑制Ras、p53蛋白的过度表达能力有关。姜黄素有望成为一种有应用前景的膀胱癌预防药物。

Objective Through observing the pathological change and the change of the Ras protein and p53 protein and cytokeratin 20（CK20） mRNA in bladder bladder tumor tissue induced by aristolochic acid, to evaluate the preventing effect of curcumin and explore the possible mechanism. Methods Fifty rats were divided into three groups randomly, control group, experiment group and preventive group. The rats in experimental group were given 10 mg/（kg·d） of aristolochic acid for 3 months; do the same to the preventive group,and at the same time,added 2% curcumin powder to intervene; the rats in the control group received normal diet and water. After three months all of the rats were sacrificed and the bladder tissue obtained,the Ras protein, p53 protein and CK20 rnRNA detected. Results After three months, the incidence of the bladder tumor of the experiment group was 95% （19/20）, while that of the preventive group was 10% （2/20）. The Ras protein and p53 protein and the CK20 mRNA in control group were negative,on the contrary, they were positive in the preventive group and the experiment group. The change of experiment group was obvious, showing statistical significance （P〈0. 001 ）. Conclusion Curcumin had a preventive effect on the bladder tumor induced by aristolochic acid. The possible molecule mechanism was that curcumin can inhibit the over expression of Ras gene and p53 gene.