L-精氨酸对实验性结肠癌的作用与机理

目的　研究L 精氨酸在Wistar大鼠实验性结肠癌中的作用及其机制。方法　用致癌物1 ,2 二甲基联苯 (DMH)每周 1次皮下注射 2 0周建立大鼠结肠癌模型 ,给予L 精氨酸溶液口服 ,对照组皮下注射EDTA ,大鼠共分为 6组 ,每组 1 8～ 2 0只。 2 2周后处死动物 ,研究肿瘤特性、全血淋巴细胞对有丝分裂素PHA的反应、T细胞亚型 (CD2 ,CD4,CD8)及血浆胃泌素浓度变化。结果　精氨酸可明显降低结肠癌的体积 ,而对结肠腺瘤则无明显差异。早期全程应用精氨酸明显减少侵犯到粘膜下层的腺癌数量 ,刺激淋巴细胞对有丝分裂素的反应并提高T细胞亚型的分布。但精氨酸不改变CD4/CD8比率以及胃泌素的浓度。结论　精氨酸降低实验性结肠癌的生成可能与其非特异性刺激机体淋巴细胞免疫功能有关 ,这种作用在肿瘤发生早期更显著。

Effect and mechanism of L-Arginine on experimental colorectal cancer

Objective The effect of arginine on chemical-induced colorectal carcinogenesis was investigated in Wistar rats. Methods Colorectal cancer was produced by weekly subcutaneous injections of carcinogen 1,2-dimethylhydrazine(DMH) for 20 weeks.Arginine was given in 1% solution either whole experimental period for 22 weeks or only during last 12 weeks. EDTA-treated animals were as controls.Tumor characteristics,peripheral lymphocyte responses to mitogen PHA,T-cell subsets(CD2,CD4,CD8)and plasma gastrin concentration were studied.Results No EDTA animals developed tumors.Adenoma areas and volumes were not different among DMH-treated animals,but adenocarcinoma areas and volumes in both arginine-fed groups were significantly reduced compared with DMH controls( P <0.02).Adenocarcinomas beyond submucosa were the lowest in the group fed arginine during whole experimental period( P <0.05).Arginine given in both EDTA-treated animals and during whole experimental period of DMH-treated animals significantly stimulated lymphocyte mitogenesis and increased T-cell subset distribution while arginine given during last 12 weeks did not.The ratio of CD4/CD8 and plasma gastrin concentration were not changed by arginine supplementation.Conclusion The reduced carcinogenesis by L-arginine might be related to its non-specific stimulation of host lymphocyte function and it is unlikely to be associated with gastrin secretion.