Role of transforming growth factor β1 in the development of atrophic gastritis

目的:探讨转化生长因子β1(transforming growth factor β1,TGFβ1)蛋白表达在幽门螺杆菌(Helicobacter pylori,H.pylori)感染相关非化生性萎缩性胃炎形成中的作用.方法:采用免疫组织化学方法,检测TGFβ1、CD68及平滑肌肌动蛋白(smooth nluscle actin,SMA)在H.pylori感染阳性的10例轻度非萎缩性胃炎,30例轻度非化生性萎缩性胃炎及32例重度非化生性萎缩性胃炎中的表达情况,且对3例轻度非萎缩性胃炎、4例轻度非化生性萎缩性胃炎进行电镜观察.结果:重度非化生性萎缩性胃炎组,每高倍视野(hish-power field,HPF)TGFβ1阳性细胞数(53±22个)显著高于轻度非化生性萎缩性胃炎组(22±9个/HPF)及轻度非萎缩性胃炎组(0-3个/HPF,P＜0.01);CD68阳性细胞数(23±7 个/HPF)显著高于轻度非化生性萎缩性胃炎组(13±6 个/HPF)及轻度非萎缩性胃炎组(0～3个/HPF,P＜0.01).TGFβ1与CD68表达的相关分析表明,在轻度及重度非化生性萎缩性胃炎组,两者均有中等程度的相关性(r=0.634,P＜0.01;r=0.699,P＜0.01).与轻度非萎缩性胃炎比较,轻度及重度非化生性萎缩性胃炎组黏膜固有层中SMA阳性的肌纤维母细胞及平滑肌细胞均增多.电镜观察轻度非萎缩性胃炎可见纤维母细胞增生,而轻度非化生性萎缩性胃炎可见大量纤维母细胞增生及肌纤维母细胞出现,并可见到纤维母细胞与肌纤维母细胞、肌纤维母细胞与平滑肌细胞并行现象.结论:TGFβ1蛋白的表达随非化生性萎缩性胃炎萎缩程度的增加而呈上升趋势,提示TGFβ1可能在非化生性萎缩性胃炎病变的发展过程中起重要作用.Objective:To investigate the role of transforming growth factor β1 (TGFβ1) in the development of Helicobacter pylori ( H. pylori)-associated non-metaplastic atrophic gastritis. Methods:The expressions of TGFβ1, CD68 and smooth muscle actin(SMA) were detected immunohistochemically in 10 patients with mild non-atrophic gastritis, 30 patients with mild non-metaplastic atrophic gastritis, and 32 patients with severe non-metaplastic atrophic gastritis having H. pylori infecion. Meanwhile, three cases of mild non-atrophic gastritis and 4 cases of severe non-metaplastic atrophic gastritis were observed with electron microscope. Results: The count of TGFβ1 positive cells per high-power field (HPF) in severenon-metaplastic atrophic gastritis group (53±22 ) was significantly higher than that in mild non-atrophic gastritis group(22±/HPF) and mild non-atrophic gastritis group(0-3/HPF, P＜0.01). The count of CD68 positive cells in severe non-metaplastic atrophic gastritis group (23±7/HPF) was significantly higher than that in mild non-atrophic gastritis group (13±/HPF) and mild non-atrophic gastritis group (0-3/HPF, P＜0. 01). Correlation analysis showed that the expressions of TGFβ1 and CD68 had a moderate correlation in each group ( r = 0. 634, P＜ 0. 01; r = 0. 699, P＜ 0. 01). Compared with mild non-atrophic gastritis, SMA-positive myofibroblasts and smooth muscle cells in the lamina propria increased in mild and severe non-metaplastic atrophic gastritis. Ultrastructurally, the proliferation of fibroblasts in gastric lamina propria was observed in mild non-atrophic gastritis, while the proliferation of fibroblasts and presence of myofibroblasts could be observed in mild non-metaplastic atrophic gastritis, and there was a parallel phenomenon between myofibroblasts and fibroblasts, as well as smooth muscle cells.Conclusion: Our findings indicate that TGFβ1 expression increases with severity of H. pylori-associated non-metaplastic atrophic gastritis, suggesting that TGFβ1 might play an important role in the development of non-metaplastic atrophic gastritis.国家高技术研究发展计划(863)计划项目; 国家重点基础研究发展计划(973)计划项目; 北京市科委新星计划中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)06635-6394