四联疗法对不同CYP2C19型幽门螺杆菌相关性胃溃疡患者基质金属蛋白酶和金属蛋白酶组织抑制剂1表达的影响

Efficacy of quadruple therapy on expression of MMP and TIMP-1 in patients with helicobacter pylorire-lated gastric ulceraccording to CYP2C19 polymorphism

目的探究四联疗法对不同CYP2C19型幽门螺杆菌(Hp)相关性胃溃疡患者基质金属蛋白酶(MMP)和金属蛋白酶组织抑制剂1(TIMP-1)表达的影响。方法回顾性分析焦作市第二人民医院2019年6月至2021年6月到院就诊的Hp相关性胃溃疡患者120例作为研究对象。根据不同CYP2C19基因型分为2组,将CYP2C19*1型患者设为对照组(60例),CYP2C19*2型患者设为观察组(60例)。所有患者均采用奥美拉唑、阿莫西林、枸橼酸铋钾、克拉霉素四联疗法。连续治疗2周后比较2组患者临床疗效以及Hp根除率,并检测2组患者抑酸起效(pH≥4)时间以及持续时间,并比较2组患者治疗前后TIMP-1以及MMP表达情况。结果观察组治疗总有效率为95%,Hp根除率为88%,均高于对照组(80%、77%),差异有统计学意义(χ^(2)=10.286,P=0.001;χ^(2)=4.715,P=0.030);观察组抑酸起效时间低于对照组,持续时间高于对照组,差异有统计学意义(t=9.437,P<0.01;t=3.275,P=0.001);2组治疗前后MMP-3、MMP-7、MMP-9以及TIMP-1表达量均降低,且治疗后观察组低于对照组,差异有统计学意义(t=2.363,P=0.020;t=7.248,P<0.01;t=5.339,P<0.01;t=5.231,P<0.01)。结论相较于CYP2C19*1型Hp相关性胃溃疡,四联疗法在CYP2C19*2型患者体内见效更快,Hp根除率更高,能抑制MMP和TIMP-1的表达,疗效更显著。

Objective To investigate the efficacy of quadruple therapy on expression of MMP and TIMP-1 in patients with helicobacter pylori(HP)-related gastric ulcer according to CYP2C19 polymorphism.Methods Retrospectively included as subjects were 120 patients with Hp-related gastric ulcer who visited Jiaozuo Second People′s Hospital between June 2019 and June 2021.According to CYP2C19 genotypes,they were divided into two groups,the patients with CYP2C19*1 genotype as the control group(n=60),and those with CYP2C19*2 genotype as the study group(n=60).All patients were treated with quadruple therapy consisting of omeprazole,amoxicillin,bismuth potassium citrate,and clarithromycin.After two consecutive weeks of treatment,the clinical efficacy and Hp eradication in the two groups were compared.The time to and the duration of acid suppression(pH≥4)were recorded for the two groups.The expression of tissue inhibitor of metalloproteinases-1(TIMP-1)and matrix metalloproteinases(MMP)before and after treatment was compared between the two groups.Results The total treatment response in was 95%,and the Hp eradication rate was 88%the study group,which were significantly higher than those in the control group(80%and 77%),with statistically significant differences(χ^(2)=10.286,P=0.001;χ^(2)=4.715,P=0.030).The study group experienced significantly shorter time to acid suppression action and longer duration of acid suppression compared with thecontrol group(t=9.437,P<0.01;t=3.275,P=0.001).The expression levels of MMP-3,MMP-7,MMP-9 and TIMP-1 were significantly reduced after treatment in either group,and these levels were significantly lower in the study group than the control group,with statistical differences(t=2.363,P=0.020;t=7.248,P<0.01;t=5.339,P<0.01;t=5.231,P<0.01).Conclusion Compared with patients with CYP2C19*1 genotye,quadruple therapy leads to earlier action,higher eradication rate,more significant suppression of MMP and TIMP-1 expression,and better efficacy in treatment of HP-related gastric ulcer among patients with CYP2C19*2 genotype.