血管生成与胃癌发生之间关系的实验研究

Relationship between gastric carcino- genesis and angiogenesis

目的:研究血管生成与胃癌发生之间的关系.方法:利用化学致癌剂N-甲基-N’-硝基-亚硝基胍(MNNG)诱发建立大鼠胃癌前病变及胃癌模型,观察胃癌发生过程中不同阶段血管生成情况,并采用抗CD34抗体的免疫组化方法显示不同癌前病变期微血管数量(MVC)变化.结果:胃黏膜腺体处于增生期,血管生成很少,至异型增生阶段,尤其是中、重度异型增生阶段或黏膜内癌时,血管生成明显增多并呈明显的异质性分布,至浸润性癌期,浸润前缘周围血管异常丰富,肿瘤组织间质也有血管生成.与增生期和轻度异型增生相比,中、重度异型增生的微血管数(MVC)明显增高(26.3±9.6vs17.1±5.6,32.5±11.7vs17.1±5.6)(P分别<0.05,0.01),但中度与重度异型增生的微血管数差别不明显.结论:血管生成在胃癌发生早期即已启动,随着病变损害向进展期发展而愈加明显,与胃癌的发生发展关系密切.

AIM:To study the relationship between gastric carcinogenesis and angiogenesis. METHODS:Experimental model of gastric precancerous lesions and carcinomas was established in rats by chemical carcinogen, N-methyl-N’-nitro-soguanidine (MNNG). The specimens were collected in groups at different time points from pre-malignant precursor to gastric carcinoma, the sections were stained by HE and angiogenesis was observed. Tissue sections were also immunohistochemically stained for CD34 antigen, a marker for endothelial cells, and the microvessels were counted. RESULTS:Only a few microvessels were found in the hyperplastic stage of gastric mucosal glands, but angiogenesis was increased markedly and heterogeneously distributed in the dysplastic stage, especially in specimens with moderate and severe degree of dysplasia as well as in the intra-mu- cosal carcinoma.Profuse vascularity in the frontier of tumor invasion and tumor stroma was found in the infiltrating carcinoma. Comparison of microvessel counts in low grade lesions (hyperplasia and mild dysplasia) with microvessel counts in moderate (26.3±9.6 vs 17.1±5.6, P <0.05) and severe dysplasia lesions ( 32.5±11.7 vs 17.1±5.6, P <0.01) showed a statistically significant increase in the more advanced lesions, but there was no significant differ- ence in vessel count between moderate and severe degree of dysplasia. CONCLUSION:Angiogenesis is switched on at the early stage of gastric carcinogenesis, and becomes more pronounced with the progress toward more advanced stage. There is aclose relationship between gastric carcinogenesis and angiogenesis.