Polo样激酶1在幽门螺杆菌感染慢性萎缩性胃炎癌前病变中的表达及意义

Expression and significance of Polo-like kinase 1 in the precancerous lesions of chronic atrophic gastritis infected by Helicobacter pylori

目的探讨Polo样激酶1(PLK1)在幽门螺杆菌(Hp)感染慢性萎缩性胃炎(CAG)癌前病变中的表达及意义。方法选取2017年1月-2021年1月在河北省廊坊市人民医院接受胃镜检查的260例患者,根据胃黏膜病理检查分为浅表性胃炎组95例、CAG伴低级别上皮内瘤变(L-IN)组70例、伴高级别上皮内瘤变(H-IN)组65例、胃癌组30例,检测各组Hp感染情况,并采用实时荧光定量聚合酶联反应检测患者胃黏膜中PLK1表达量。取人胃上皮细胞GES-1,采用完全随机化方式分为空白组、对照组、BI2536组,空白组不做处理,对照组、BI2536组建立Hp与GES-1细胞共培养模型。对照组加入正常DMEM培养基培养,BI2536组加入终浓度为20 nmol/L的BI2536S培养。二甲基噻唑(MTT)实验检测增殖能力;AnnexinV/PI双染法检测凋亡能力。结果与浅表性胃炎组和CAG伴L-IN组比较,CAG伴H-IN组及胃癌患者胃黏膜PLK1表达量升高,且胃癌组高于CAG伴H-IN组(P<0.05);浅表性胃炎组和CAG伴L-IN组比较胃黏膜PLK1表达量无差异(P>0.05)。与Hp阴性CAG患者比较,Hp阳性CAG患者PLK1表达量升高(P<0.05)。与Hp阳性浅表性胃炎组和CAG伴L-IN组比较,Hp阳性CAG伴H-IN组及胃癌患者胃黏膜PLK1表达量升高,且胃癌组高于CAG伴H-IN组(P<0.05);Hp阳性浅表性胃炎组和CAG伴L-IN组比较胃黏膜PLK1表达量无差异(P>0.05)。与空白组比较,对照组、BI2536组细胞PLK1表达量升高,且对照组高于BI2536组(P<0.05)。与空白组比较,对照组24、48、72 h三个时刻MTT实验A值均降低,凋亡率升高(P<0.05);与对照组比较,BI2536组24、48、72 h三个时刻MTT实验A值均升高,凋亡率降低(P<0.05)。结论胃黏膜PLK1表达量在Hp感染的CAG癌前病变进程中逐渐升高。PLK1抑制剂BI2536可显著降低Hp对人胃上皮细胞GES-1增殖的抑制作用,并抑制GES-1细胞凋亡。

Objective To study the expression and significance of Polo-like kinase 1(PLK1)in the precancerous lesions of chronic atrophic gastritis(CAG)infected by Helicobacter pylori(Hp).Methods 260 patients underwent gastros⁃copy in the People's Hospital of Langfang City,Hebei Province from January 2017 to January 2021 were selected.Ac⁃cording to the pathological examination of gastric mucosa,they were divided into superficial gastritis group(n=95 cas⁃es),CAG with low-grade intraepithelial neoplasia(L-IN)group(n=70 cases),CAG with high-grade intraepithelial neo⁃plasia(H-IN)group(n=65 cases),gastric cancer group(n=30 cases).The Hp infection of each group was detected,and the expression of PLK1 in the gastric mucosa of patients was detected by real-time fluorescence quantitative poly⁃merase-linked reaction.The PLK1 protein expression in gastric mucosa was detected by western blot.Human gastric epithelial cells(GES-1)were randomly divided into blank group,control group and BI2536 group.The blank group was not treated,the control group and the BI2536 group were established a co-culture model of Hp and GES-1 cells.The control group was cultured with normal DMEM medium,and the BI2536 group was cultured with BI2536S at a fi⁃nal concentration of 20 nmol/L.The proliferative ability were detected by dimethylthiazole(MTT)experiment.The apoptosis ability was detected by Annexin V/PI double staining method.Results Compared with the superficial gastri⁃tis group and the CAG with L-IN group,the relative expression of PLK1 in the gastric mucosa of the CAG with H-IN group and gastric cancer patients increased,and the gastric cancer group was higher than the CAG with H-IN group(P<0.05).There was no difference in the relative expression of PLK1 in the gastric mucosa between the superficial gas⁃tritis group and the CAG with L-IN group(P>0.05).The relative expression of PLK1 in Hp-positive CAG patients was higher than that of Hp-negative CAG patients(P<0.05).Compared with the Hp-positive superficial gastritis group and the CAG with L-IN group,the relative expression of PLK1 in the gastric mucosa of the Hp-positive CAG with H-IN group and gastric cancer patients increased,and the gastric cancer group was higher than the CAG with H IN group(P<0.05).There was no difference in the relative expression of PLK1 in the gastric mucosa between the su⁃perficial gastritis group and the CAG with L-IN group(P>0.05).Compared with the blank group,the expression of PLK1 of the control group and BI2536 group were increased,and the control group was higher than that of the BI2536 group(P<0.05).Compared with the blank group,the MTT test A value of the control group were decreased at 24,48,and 72 h,of which the apoptosis rate was increased(P<0.05).Compared with the control group,the MTT test A value of the BI2536 group were decreased at 24,48,and 72 h,of which the apoptosis rate was decreased(P<0.05).Conclu⁃sion The expression of PLK1 in gastric mucosa gradually increases in the course of CAG precancerous lesions infected by Hp.BI2536(PLK1 inhibitor)can significantly reduce the inhibitory effect of Hp on the proliferation of GES-1 and inhibit the apoptosis of GES-1 cells.