胃癌及癌前病变细胞增殖和凋亡与bcl-2/bax表达的关系

Relationship between the expression of bcl-2/bax gene and cell apoptosis and proliferation in gastric cancer and its pre-cancerous lesions

目的：观察细胞凋亡和增殖及其调控基因在胃癌及癌前病变发生发展过程中的异常变化 ,探讨细胞凋亡在胃癌演变中的作用。方法：对 128例胃癌及癌前病变患者和正常人 ,采用原位末端标记法 (terminal deoxynucleotidly transferase mediated labelling， TUNEL)及免疫组化技术检测胃粘膜上皮细胞凋亡、增殖及 bcl- 2/bax表达。结果：正常人、浅表性胃炎、萎缩性胃炎、肠上皮化生、不典型增生、胃癌的细胞凋亡指数分别依次为 (4.58± 1.92)％、 (10.14± 2.56)％、 (24.6± 35.19)％、 (26.26± 9.34)％、 (19.35± 4.04)％、 (19.81± 4.66)％ ;PCNA指数分别为 (3.93± 1.02)％、 (13.58± 4.65)％、 (20.16± 4.89)％、 (24.30± 4.44)％、 (39.79± 6.37)％、 (54.79± 10.6)％ ; bcl- 2蛋白表达分别为： 0％、 18.6％、 20％、 38.5％、 44.4％、 58.3％ ;bax蛋白表达分别为 20％、 51.2％、 55％、 30.85％、 27.8％、 16.7％。结论：胃粘膜癌变过程中 ,起初三个阶段细胞凋亡和 PCNA同时增加 ,而至肠化生后 ,细胞凋亡指数显著减少， PCNA指数显著增加 ;凋亡调控基因 bcl- 2和 bax的比值逐渐增加 ,尤其肠化生阶段后增加显著 ,说明在胃癌演变过程中它们起重要作用 ,临床防治胃癌发生应从肠化生之前着手。

Objective： The current study was designed to investigate the role of apoptosis and proliferation in the pathogenesis of gastric carcinoma. Methods： Using terminal deoxynucleotidly transferase mediated nick labelling(TUNEL) technique, histochemistry and immunohistochemistry methods, the cells apoptosis and PCNA indexes, bcl- 2 and bax protein were examined in 10 normal gastric mucosa, 43 chronic active supperticial gastritis, 20 chronic atrophic gastritis, 13 intestinal metaplasia, 18 gastric dysplasia and 24 gastric carcinomas. Results： In the normal group and the patients of chronic superficial gastritis, atrophic gastritis, intestinal metaplasia, gastric dysplasia and gastric carcinomas, their apoptosis indexes were (4.58± 1.92)％ ,(10.14± 2.56)％ ,(24.6± 35.19)％ ,(26.26± 9.34)％ ,(19.35± 4.04)％ and (19.81± 4.66)％ , respectively; PCNA indexes were (3.93± 1.02)％ , (13.58± 4.65)％ , (20.16± 4.89)％ ,(24.30± 4.44)％ , (39.79± 6.37)％ , and (54.79± 10.6)％ respectively; the expression of bcl- 2 were 0％ ,18.6％ ,20％ ,38.5％ ,44.4％ and 58.3％ , respectively; the expression of bax were 20％ ,51.2％ , 55％ , 30.85％ , 27.8％ and 16.7％ , respectively. Conclusion： The present results indicate that the apoptosis and proliferating indexes are increased simultaneously in normal subjects, chronic superficial gastritis, atrophic gastritis and intestinal metaplasia; However, apoptosis indexes are decreased, but PCNA indexes are increased continuously in dysplasia and carcinoma; The ratio of bcl- 2 and bax expression are showed negative correlation with apoptosis. These results further suggest that prevention of development of gastric carcinoma should be started before occurring of intestinal metaplasia.