根除幽门螺杆菌对端粒酶相关基因及c-myc蛋白表达的影响

Effect of eradication of Helicobacter pylori on the expression of telomerase-associated genes and c-myc protein

目的 研究幽门螺杆菌 (Hp)根除前后端粒酶相关基因及c myc蛋白表达的变化 ,分析端粒酶催化亚单位 (hTERT)、端粒酶RNA(hTR)及c myc蛋白表达的关系。 方法 采用RNA原位核酸杂交和免疫组化法对 39例Hp阳性患者根除治疗及 2 1例Hp阴性患者对症治疗前后hTR、hTERT及c myc蛋白表达进行原位观察和比较。 结果 治疗前Hp阳性者hTR、hTERT及c myc蛋白阳性率显著高于Hp阴性者 (5 1.3%比 19.0 % ,5 3.8%比 2 3.8% ,5 3.8%比 2 8.6 % ,P <0 .0 5 )。Hp根除者治疗后hTR、hTERT及c myc蛋白阳性率较治疗前显著下降 (5 5 .5 %比 2 2 .2 % ,5 9.3%比 2 2 .2 % ,5 9.3%比14 .8% ,P <0 .0 5 ) ,且与Hp阴性对照组相比差异无显著性 ;而Hp未根除者及Hp阴性对照组治疗前后上述指标阳性率变化差异均无显著性 (P >0 .0 5 )。治疗前hTERT与hTR、hTERT与c myc蛋白表达均呈显著正相关 ,秩相关系数rs 分别为 0 .4 5和 0 .4 7(P <0 .0 1)。结论 Hp感染可通过诱导c myc蛋白过度表达使hTERT表达上调 ,导致端粒酶激活 ,使胃黏膜易于癌变。根除Hp可使端粒酶相关基因及c myc蛋白表达下降或消失 ,从而降低胃黏膜癌变的危险性。

Objective To investigate the expression of telomerase-associated genes and c-myc protein before and after eradication of Helicobacter pylori(H.pylori) and to elucidate the possible correlation between human telemerase catalytic subunit(hTERT) and human telomerase RNA(hTR) and c-myc protein. Methods Thirty nine H.pylori positive and 21 negative patients were enrolled. The expression of hTR,hTERT and c-myc protein before and after H.pylori eradication were compared. The expression of hTR was determined by in situ RNA hybridization whereas hTERT and c-myc protein were detected by immunohistochemical staining. Results Before treatment,the positive expression of hTR,hTERT and c-myc protein in H.pylori -positive group were significantly higher than those in H.pylori -negative group(51.3% vs. 19.0%,53.8% vs. 23.8% ,53.8% vs. 28.6%,P <0.05). There were significant correlations between hTERT and hTR( r s= 0.45 ,P <0.01),and between hTERT and c-myc protein ( r s=0.47,P <0.01). The expression of hTR,hTERT and c-myc protein were decreased significantly after H.pylori eradication than those before treatment (55.5% vs. 22.2%, 59.3% vs. 22.2%,59.3% vs. 14.8%,respectively,P <0.05),and no difference was found between H.pylori -eradicated and H.pylori -negative groups. There was no difference of all three parameters between H.pylori uneradicated and H.pylori -negative patients ( P >0.05). Conclusions H.pylori infection may upregulate the expression of hTERT by inducing the overexpression of c-myc protein,which can cause telomerase activation and gastric carcinogenesis. The expression of telomerase-associated genes and c-myc protein may decrease or disappear after H.pylori eradication,which can lower the risk of gastric carcinogenesis.