MNNG诱发大鼠胃癌与间质血管的反应

Gastric carcinogenesis and reactivity of microvessel induced by N-methlN′-nitro-N-nitrosoguanidine (MNNG) in rats

目的研究胃癌发生中，间质血管反应的意义．方法应用Ｎ甲基Ｎ硝基Ｎ亚硝基胍（ＭＮＮＧ）＋表面活性剂，对Ｗｉｓｔａｒ雄性大鼠进行诱癌实验．将ＭＮＮＧ溶于蒸馏水中，浓度为１５０ｍｇ／Ｌ，供雄性Ｗｉｓｔａｒ大鼠（ｎ＝１５０）自由吸饮．每８ｗｋ处死大鼠７只，至３２ｗｋ实验全部结束．采用主动脉灌注墨汁观察组织间微血管密度，同时采用血管内皮细胞生长因子（ＶＥＧＦ）和增生细胞核抗原（ＰＣＮＡ），以观察血管内皮细胞的反应．结果８ｗｋ～１６ｗｋ粘膜基部血管密度增加，血管内皮细胞明显增生，至２４ｗｋ发生原位癌，以ＭＮＮＧ＋ＶｉｔＤ（５０ｍｇ）组的腺胃癌发生率最高，３２ｗｋ处死的２０只大鼠中有１６只大鼠发生原位癌和润癌，肿瘤发生率为８０％．结论血管新生及血管内皮细胞增生与肿瘤生长的速度密切相关，间质组织中血管密度越大，内皮细胞增生越明显，癌细胞生长的速度越快．

IM To study the reactivity of microvessel in gastric carcinogenesis.METHODS Gastric carcinogenesis in rats was induced by topical administration of MNNG (150mg L-1) in drinking water. Four weeks after MNNG exposure, rats were swichted to the diet containing 1, 25dihydroxyvitamin D3[1,25(OH)2D3, 25mg·kg-1 and 50mg·kg-1]. Animals were killed at week 8, 16,24 and 32 for immunohistochemical study of vascular endothelial cell growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) and histopathological investigation.RESULTS At week 8 and 16, microvessel density in gastric mucosa increased and endothelial cells of the microvessls markedly proliferated.CONCLUSION The increased microvessel density is closely related to the severity of carcinogenesis. 1, 25(OH)2D3 does not inhibit, but stimulate carcinogenesis induced by MNNG