氨基胍对小鼠移植性胃癌的影响

目的：研究诱导型一氧化氮合酶（iNOS）选择性抑制剂氨基胍（AG）对皮下接种MFC胃癌细胞株小鼠的抑瘤作用，探讨其抑瘤机制。方法：50只皮下接种MFC胃癌细胞株小鼠动物模型，随机分为5组。接种后24 h开始，分别给予生理盐水（阴性对照组）、丝裂霉素组（每周注射2次，每次0.7 mg•kg^-1，MMC组）、小剂量AG组（50 mg•kg^-1•d^-1，AG_L组）、大剂量AG组（150 mg•kg^-1•d^-1，AG_H组）、丝裂霉素与AG联合给药组（MMC 每周注射2次，每次0.7 mg•kg^-1，AG_H150 mg•kg^-1•d^-1， MMC+AG_H组）。均采用腹腔内注射，2周后处死动物剥离肿瘤，称重并计算抑瘤率；应用Greiss反应法测定荷瘤动物血浆中NO含量；HE和免疫组化（SP法）染色，分别计数微血管密度（MVD）、iNOS和血管内皮生长因子（VEGF）阳性率，分析它们与AG抑瘤效应之间的关系。结果：联合用药组抑瘤率为52.9%，AG_H组为47.1%。联合用药组MVD为（8.8±2.6）%，AG_H组为（21.2±12.4）%，显著低于对照组（P<0.01）。联合用药组VEGF阳性率为（2.1±1.4）%，AG_H组为（4.8±1.6）%，同对照组比较差异有显著性（P<0.01）。联合用药组iNOS阳性率为（2.4±1.1）%，AG_H组为（3.8±0.9）%，同对照组比较差异有显著性（P<0.01）。对照组血浆中NO含量为（46.6±2.3）μmol•L^-1,AG_H组为（12.9±2.0）μmol•L^-1,差异有显著性（P<0.01）。结论：AG通过抑制iNOS活性,减少NO的生成,阻断其效应途径及VEGF的产生，抑制肿瘤血管增殖，导致肿瘤坏死增加，且对化疗药物起协同作用。亦从肿瘤间质血管方面间接证实了VEGF和iNOS是促进肿瘤血管生成的重要因子。

Effects of aminoguanidine on transplantation stomach cancer in mice

Objective To investigate the inhibitory effects of aminoguanidine(AG),a selective inhibitor of inducible nitric oxide synthase(iNOS), on mice stomach cancer and its′mechanism. Methods The mice stomach cancer cell lines MFC were implanted subcutaneously in Kunming mice.Fifty mice were randomly divided into 5 groups: Control group (saline solution), MMC group (Mitomycin, twice a week 0 7 mg·kg -1 i p ),low dosage AG group (AG L, 50 mg·kg -1 ·d -1 i p ), high dosage AG group (AG H, 150 mg·kg -1 ·d -1 i p ) and combined treatment of both MMC and high dosage AG group(MMC+AG H).All drugs were given by intraperitoneal injection. Two weeks after implantation, the mice were sacrificed, and the tumor weight,inhibitory rates,intratumoral microvessel density (MVD),the positive rate of vascular endothelial growth factor (VEGF) and iNOS were evaluated,respectively. In addition,serum were collected and nitrite levels were tested using Greiss assay. Results Compared with the negative control group,the growth of the orthotopically implanted tumor was significantly inhibited due to the reduced weight and the inhibitory rates of tumor in AG H group and MMC+AG H group were 47 1% and 52 9%,respectively. The MVD was decreased significantly in MMC+AG H group and AG H group [(21 2±12 4)% and (8 8±2 6)%],compared with control group [(68 3±10 6)%] ( P <0 01). The positive rates of VEGF and iNOS in negative control group were (10 3±1 6)% and (11 3±1 3)%. However,they were (4 8±1 6)%,(3 8±0 9)% and (2 1±1 4)%,(2 4±1 1)% in AG H group and MMC+AG H group,respectively.Conclusion AG can significantly restrain the development of mice stomach cancer through inhibiting the expression of iNOS,VEGF and decreasing MVD. Combination treatment can improve the inhibitory effect.