胃黏膜细胞线粒体DNA不稳定及核内整合与幽门螺杆菌感染有关

目的：线粒体DNA（mtDNA）因缺乏组蛋白保护，且损伤修复系统不健全，容易为幽门螺杆菌（Hp）相关胃炎中氧自由基的重要靶点，为此探讨胃黏膜细胞线粒体DNA不稳及核内整合与Hp感染的关系。方法：采用PCR和Giemsa染色检测Hp；采用限制性片段多态性（PCR－SSCP）和原位杂交方法检测胃黏膜细胞线粒体DNA微卫星不稳定（mtMSI）及核内mtDNA序列。结果：30例胃癌检出mtMSI11例（36．7％），15例肠化中有2例（13．3％），10例异型增生中有2例，10例萎缩性胃炎中有1例检出mtMSI。胃癌细胞核内mtDNA序列的检出率为20．0％（6／30），异型增生为1／10例，肠上皮化生为6．7％（1／15），萎缩性胃炎为1／10例，胃黏膜细胞mtMSI及核内mtDNA序列的检出率在Hp感染组（12／39，8／39）显著高于非Hp感染组（4／36，1／36，P＜0．05）。虽cagA^ 组mtMSI及核内mtDNA序列检出率（10／25，6／25）高于cagA^-组（2／14，2／14），但两组mtMSI及核内mtDNA序列检出率比较，差异并无显著性（P＞0．05）。结论：胃黏膜细胞mtMSI及mtDNA序列核内整合可能与Hp感染有关，并参与胃癌的发生。

Mitochondrial DNA instability and integration of mtDNA in the nuclei of gastric mucosa related to Helicobacter pylori infection

Objective Mitochondrial DNA (mtDNA) may be the target of oxygen free radicals related to Helicobacter pylori (H.pylori) infection, partly because of lack of protective histones and partly because of inefficient DNA repair systems. In this study we investigated the relationship between mitochondrial microsatellite instability (mtMSI) as well as integration of mtDNA in the nuclei of gastric mucosa and H.pylori infection. Methods H.pylori was detected using PCR and modified Giemsa staining. The mtMSI and the sequences of mtDNA in the nuclei were detected by PCR SSCP and in situ hybridization. Results The mtMSI was detected in 11 of 30 (36.7%) cases of gastric cancers, 2 of 15(13.3%) of intestinal metaplasia, 2 of 10 of dysplasia and 1 of 10 of chronic atrophic gastritis. The integration of mtDNA in the nuclei was detected in 20.0% (6/30) of gastric cancer, 1/10 of dysplasia, 6.7%(1/15)of intestinal metaplasia and 1/10 of chronic atrophic gastritis. The frequencies of mtMSI and integration of mtDNA in H.pylori positive group (12/39 and 8/39) were each significantly higher than those in H.pylori negative group (4/36 and 1/36, P <0.05). Although not statistically significant( P >0.05), mtMSI and integration of mtDNA in the nuclei tended to occur in gastric mucosa with cagA positive H.pylori infection(10/25,6/25), but less often to occur in gastric mucosa with cagA negative H.pylori infection(2/14, 2/14). Conclusions The mtMSI and integration of mtDNA may be involved in the carcinogenesis of gastric mucosa and H.pylori infection might contribute to the mtMSI and integration of mtDNA.