目的 研究苦参碱与氧化苦参碱对炎症相关结直肠癌的化学预防作用。方法 采用氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)模拟炎症相关的结直肠癌的发生发展过程。将小鼠分成对照组、模型组、苦参碱组与氧化苦参碱组,实验结束后处死小鼠,取出结直肠,统计肿瘤发生率;病理切片观察肿瘤的发生程度、免疫组化法检测结肠组织中增殖细胞核抗原(PCNA)的表达情况;Western blotting法检测结直肠组织中环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、核转录因子-κB(NF-κB)、P53和γH2AX蛋白表达情况。结果 对照组无肿瘤发生,模型组、苦参碱组与氧化苦参碱组均有肿瘤发生,但肿瘤发生程度不同。苦参碱与氧化苦参碱能够降低PCNA的表达而抑制肿瘤细胞的增殖,同时降低COX-2、iNOS、NF-κB、P53与γH2AX蛋白的表达。结论 苦参碱与氧化苦参碱均能减缓肿瘤的发展进程,降低肿瘤的严重程度,具有一定的化学预防作用;同时能对溃疡性结直肠炎进行有效干预,减缓肿瘤的发生程度甚至降低肿瘤的发生率。

Objective To study the chemoprevention of matrine and oxymatrine on the inflammation related colorectal cancer. Methods The occurrence and development of the inflammation related colorectal cancer was established by AOM/DSS. The mice were divided into blank group, control group, matrine group, and oxymatrine group, at the end of the experiment, the mice were sacrificed and the colon and rectum were harvested, and tumor incidence was calculated. The occurrence degree of tumor was observed by pathological section; The expression of proliferating cell nuclear antigen (PCNA) in colorectal tissue was detected by immunohistochemistry; The expression of COX-2, iNOS, NF-κB, p53, and γH2AX in colorectal tissue was detected by Western blotting method. Results There was no tumor occured in the blank group, while the control group, matrine group, and oxymatrine group had tumor occurrence, but the degree of tumor was different. Matrine and oxymatrine could inhibit the proliferation of tumor cells, and decrease the expression of NF-κB, P53, COX-2, iNOS, and γH2AX. Conclusion Matrine and oxymatrine could slow down the development of colorectal carcinoma, reduce the severity of colorectal cancer, and have a certain preventive effect. Taking an effective intervention in ulcerative colitis, the development of colorectal carcinoma can be slowed down and even the incidence can be reduced.

国家自然科学基金资助项目(81073059)