不同病变胃粘膜端粒酶活性及其亚单位的检测

目的：探讨端粒酶及其亚单位（ＴＰ１、ｈＴＲ、ｈＴＲＴ）在胃粘膜癌变过程中的作用。方法：端粒酶的检测采用端粒末端重复序列扩增技术（ｔｅｌｏｍｅｒｉｃ　ｒｅｐｅａｔ　ａｍｐｌｉｆｉｃａｔｉｏｎ　ｐｒｏｔｏｃｏｌ，ＴＲＡＰ），端粒酶亚单位的检测采用ＲＴ－ＰＣＲ法。结果：端粒酶阳性检出率在慢性萎缩性胃炎、肠上皮化生、异型增生及胃癌中分别为２４．６％（１４／５７）、３８．９％（７／１８）、３７．５％（３／８）及９２．３％（６０／６５），正常胃粘膜未检测到端粒酶活性，与以上各病变组织有显著性差异（Ｐ＜０．０５～０．０１），而慢性萎缩性胃炎、肠上皮化生和异型增生组织中端粒酶阳性率亦明显低于胃癌组织（Ｐ＜０．０１）；端粒酶的表达与临床病理指标无相关性；ＲＴ－ＰＣＲ定性检测发现端粒酶亚单位ｈＴＲ和ＴＰ１在大多数胃粘膜中都有表达，而ｈＴＲＴ主要在胃癌及部分癌前组织中表达，且在胃癌中ｈＴＲＴ的表达与端粒酶活性之间具有明显的相关性（Ｐ＜０．０１）。结论：端粒酶不仅在胃癌组织中高表达，在部分癌前组织中也有表达。提示端粒酶在胃癌的发生过程中可能具有重要作用；端粒酶亚单位ｈＴＲＴ不仅可能作为胃癌的诊断指标，而且还可能作为胃癌基因治疗的靶

Determination of Telomerase Activity and its Subunits in Different Gastric Lesions

Objective: The current study was designed to explore the role of telomerase and its subunits in the process of gastric carcinogenesis. Methods: Telomerase activity was detected with telomeric repeat amplification protocol (TRAP) and its subunits were examined by RT-PCR. Results: Telomerase activity was noted positive in 24. 6% (14/57) for chronic atrophic gastritis, 38.9% (7/18) for intestinal metaplasia, 37.5% (3/8) for dysplasia and 92.3% (62/65) for gastric carcinoma, respectively. On the contrary, no telomerase activity was detected in normal mucosa. The frequency of telomerase activity in gastric carcinoma was significantly higher than that in chronic atrophic gastritis, intestinal metaplasia and dysplasia (P < 0. 01). Telomerase activity in gastric carcinoma was not related with clinicopathological parameters. Telomerase subunits, TP1 and hTR, were expressed in most gastric mucosas and no significant difference was found among different groups. However, another telomerase subunit, hTRT, was mainly detected in gastric carcinoma and partially premalignant lesions or diseases and the expression of hTRT paralleled to the expression of telomerase. Conclusions: Telomerase activitymay play an important role in the early stage of gastric carcinogenesis. hTRT may be not only a good diagnostic parameter but also a target for gene therapy in gastric cancer because hTRT expression parallels to telomerase activity.