5-氨基乙酰丙酸诱导卟啉代谢物在大肠癌大鼠尿液中积聚的研究

Accumulation of porphyrin metabolites induced by 5-aminolevulinic acid in urine of rats with colorectal cancer

目的探讨5-氨基乙酰丙酸(ALA)诱导卟啉代谢物[尿卟啉原(UP)Ⅰ和粪卟啉原(CP)Ⅲ]在大肠癌大鼠尿液中的积聚。方法采用二甲基肼建立大鼠大肠癌模型。收集30只大肠癌大鼠(大肠癌组)和30只正常大鼠(正常组)的尿液。每只灌胃给药5-ALA(50 mg/kg),2、4、6、8 h后留取尿液。用高效液相色谱法检测尿液中卟啉代谢产物UPⅠ和CPⅢ的含量,比较其含量在各组大鼠中的差异。结果在口服5-ALA前,大肠癌组和正常组尿液中UPⅠ和CPⅢ的含量差异无统计学意义(P>0.05),口服5-ALA后大肠癌组尿液中UPⅠ和CPⅢ的含量较正常组明显升高(P<0.05),4 h测得大肠癌组尿液中UPⅠ和CPⅢ含量达最高值。根据4 h检测结果绘制ROC曲线,UPⅠ诊断大肠癌的阈值为50.43μmol/g,灵敏度为96.7%,特异度为63.3%;CPⅢ诊断大肠癌的阈值为108.85μmol/g,灵敏度为66.7%,特异度为86.7%。结论5-ALA诱导卟啉代谢物在大肠癌大鼠尿液中的积聚显著,尿液中卟啉代谢物可能为一种新的大肠癌肿瘤标志物,可为结直肠癌的诊断提供实验依据。

Objective To investigate the accumulation of porphyrin metabolites[uroporphyrinogen(UP)Ⅰand coproporphyrinogen(CP)Ⅲ]induced by 5-aminolevulinic acid(5-ALA)in the urine of rats with colorectal cancer.Methods The rat model of colorectal cancer was established by dimethylhydrazine(DMH).Urine samples were collected from 30 colorectal cancer rats(colorectal cancer group)and 30 normal rats(normal group).Each animal was given 5-ALA(50 mg/kg)by gavage,and urine was collected after 2,4,6 and 8 h.The contents of urinary porphyromogenⅠand porphyromogen faecalisⅢin urine were detected by high performance liquid chromatography(HPLC).Results There was no significant difference in the contents of UPⅠand CPⅢin urine between colorectal cancer group and normal group before oral administration of 5-ALA(P>0.05).After oral administration of 5-ALA,the contents of UPⅠand CPⅢin urine of colorectal cancer group were significantly higher than those of normal group(P<0.05).The contents of UPⅠand CPⅢin urine of colorectal cancer group reached the highest value at 4 hours.According to the receiver operating characteristic(ROC)curve drawn from 4-hour test results,the threshold value of UPⅠfor colorectal cancer diagnosis was 50.43μmol/g,with corresponding sensitivity 96.7%,and the specificity 63.3%,respectively.The threshold value of CPⅢfor colorectal cancer diagnosis was 108.85μmol/g,with corresponding sensitivity 66.7%,and the specificity 86.7%,respectively.Conclusions The accumulation of porphyrin metabolites induced by 5-ALA in the urine of rats with colorectal cancer is significant.The porphyrin metabolites in urine may be a new tumor marker of colorectal cancer,which provides an experimental basis for the diagnosis of colorectal cancer.