叶绿酸铜钠对结直肠肿瘤抑制作用的实验研究

Restraining effect of Sodium Copper Chlorophyllin on colorectal cancer of mice

目的：研究叶绿酸铜钠（CHL）对DMH（1,2-二甲基肼二盐酸盐）诱导的小鼠结直肠肿瘤的抑制作用。方法：80只幼鼠（4-5周）随机分为阴性对照组（NC组）、阳性对照组（DMH组）、CHLA组和CHLB组。DMH组和CHL组背部皮下注射DMH诱癌;NC组背部皮下注射生理盐水作对照。以CHL灌胃处理CHLA和CHLB组动物。处死小鼠后,解剖小鼠结直肠,固定,观察肿瘤发生情况,免疫组化染色示PCNA、Ras-p21及caspase-3等细胞增殖及凋亡相关因子的表达情况。结果：两CHL干预组小鼠结直肠肿瘤发生率与DMH组相比,差异无统计学意义（P〉0.05）;但其平均每鼠荷瘤数及结直肠癌百分率都显著低于DMH组（P〈0.05）;不同时间CHL干预对小鼠肿瘤的抑制作用差别不明显（P〉0.05）;两CHL干预组小鼠肠黏膜PCNA、Ras-p21蛋白表达水平均显著低于DMH组（P〈0.01）;caspase-3表达水平在DMH和CHL组间无明显差异（P〉0.05）。结论：CHL在诱癌起始阶段和始发后阶段给药均可抑制DMH诱导的小鼠结直肠肿瘤的发生,降低每鼠平均荷瘤数及肠癌百分率,这可能与其下调结直肠黏膜PCNA,Ras-p21水平,从而间接调控细胞增殖和凋亡平衡有关,CHL有望成为预防结直肠癌的理想化学制剂。

Objective： To research possible restraining effect of sodium copper chlorophyllin （CHL） on DMH-induced colorectal tumour in mice.Methods： 80 mice （male） （4-5 weeks ） were randomly divided into negative control group （NC group, in which the mice were given hypodermic injection of physiological saline）, DMH group, CHLA group and CHLB group（the mice in these three groups were given hypodermic injection of DMH on the back ,those in CHL group were given CHL intragastric administration）.The whole colon and rectum were dissected to observe shape and distribution of large bowel tumour, marked with number, fixed and immunohistochemistry stains. Results：There was no significant difference between incidence of colgrectal carcinoma of CHL group and DMH group （P〉0.05）. While incidence of colorectal cancer, average number of tumour, and the percentage of carcinoma in these tumours of CHL group were all significantly lower than those of DMN group （P〈0.05）. There was no significant difference between effect of CHLA group and CHLB group （P〉0.05）. In further mechanism exploration, PCNA and Ras-p21 expression level of CHL treated groups were both found to be elevated than those of DMH group （P〈0.01）, while expression level of caspase-3 were found to be unchanged by CHL （P〉0.05） treatment.Condusion：CHL can suppress the incidence of DMH-induced colorectal tumour in mice, whether it is given at the initiation or in the middle of DMH treatment. This effect may be partly attributed to CHL＇s reducing effect on PCNA and Ras-p21 expression and the subsequent suppression effect on excessive cell proliferation.