和中健脾方对PPI依赖性GERD患者胃肠激素和炎症因子的表达及PPI撤减模式的临床探索观察

Clinical observation of Hezhong Jianpi Formula on the expression of gastrointestinal hormones and inflammatory factors in patients with PPI dependent GERD and the mode of PPI withdrawal

目的:观察和中健脾方在质子泵抑制剂(PPI)撤减过程中的作用及患者体内胃肠激素和炎症因子的表达水平,为临床治疗对PPI产生依赖性的胃食管反流病(GERD)患者提供新的用药思路及方案。方法:采集63例GERD患者的资料,随机分为两组:治疗组31例、对照组32例。治疗组患者在服用维持剂量PPI的情况下,依照和中健脾法辨证施治后加服以和中健脾方为主方化裁的中药,并根据每两周GERD临床症状观察表的评分进行逐步撤减西药;对照组患者根据原来PPI维持剂量继续服用。两组总观察周期为22周,分别在入组时、治疗4周时测定胃肠激素(VIP、GAS、MOT)及炎症细胞因子(IL-6、IL-8、TNF-α)指标变化。之后进行18周的PPI撤药过程,观察其治疗前后的总体疗效、症状积分表及相关的胃镜变化;统计PPI治疗后的用量与起始治疗时的相差剂量。结果:治疗组总体症状积分的改善明显优于对照组(P<0.05)。治疗组整个治疗过程中PPI的使用总剂量明显少于对照组(P<0.05)。对治疗组症状作LSD多重比较显示,在前10周PPI依赖性患者在加服中药和中健脾方后于相邻周数的症状积分比较上差异无统计学意义(P>0.05),而在周数相差较大的区域中,症状积分均有明显的差异变化(P<0.05)。对治疗组行撤减完成周数百分比统计,患者完成撤减周数从10周开始,且例数最多,12~18周完成撤减例数的百分比逐渐下降。对治疗组PPI剂量作LSD多重比较显示,后期的PPI剂量变化差异无统计学意义(P>0.05),而在前10周根据每两周的症状积分评估,患者的PPI剂量差异有统计学意义(P<0.05)。治疗组能有效改善患者GAS、VIP、MOT的表达水平;对照组能改善患者VIP、MOT的表达水平,而GAS的表达水平治疗前后差异无统计学意义;治疗后组间比较,治疗组能更有效改善VIP、MOT的表达水平,而两组GAS的改善水平差异无统计学意义;治疗组和对照组均能有效改善患者IL-6、IL-8、TNF-α的表达水平;治疗后组间比较差异有统计学意义。临床运用和中健脾方未发现不良反应。结论:在GERD临床症状观察表评分疗效为显效的基础上,和中健脾方能有效促进对PPI产生依赖性患者临床症状的改善及其PPI剂量的逐步减量。和中健脾方能更有效改善患者胃肠激素VIP、MOT的表达及炎症因子的表达,可能是其潜在的作用机制;和中健脾方联合PPI减量治疗期间未发现不良反应,安全性及临床实用价值高。

Objective:To observe the effect of Hezhong Jianpi Formula on proton pump inhibitors(PPI)withdrawal and the expression levels of gastrointestinal hormones and inflammatory factors in patients with gastroesophageal reflux disease(GERD)dependent on PPI,so as to provide new medication ideas and schemes for clinical treatment of patients with GERD dependent on PPI.Methods:Sixty-three cases were collected.All cases were confirmed as gastroesophageal reflux disease according to the diagnostic criteria of GERD.These patients have been treated with PPI regularly,and now they rely on PPI to maintain the stability of symptoms.The patients were randomly divided into two groups:31 cases in the treatment group and 32 cases in the control group.For the patients in the treatment group of integrated Traditional Chinese and Western medicine,that is,under the condition of taking proton pump inhibitor of maintenance dose,the Traditional Chinese Medicine with Hezhong Jianpi Formula as the main prescription was added after treatment according to the syndrome differentiation and treatment of Hezhong Jianpi Formula,and the western medicine was gradually withdrawn according to the score of clinical symptom observation table of gastroesophageal reflux disease every two weeks;for patients in the control group,they continued to take the original PPI maintenance dose.Gastrointestinal hormones(VIP,GAS,MOT)and inflammatory cytokines(IL-6,IL-8,TNF-α)were measured at the time of enrollment and 4 weeks of treatment.After another 18 weeks,PPI withdrawal was started,and the overall efficacy,symptom score table and gastroscopy changes of related patients were observed before and after treatment;the difference between the dosage after PPI treatment and the initial treatment was counted.Results:The total symptom score of the treatment group was significantly better than that of the western medicine maintenance control group(P<0.05).The total dosage of PPI in the treatment group was significantly less than that in the control group(P<0.05).LSD multiple comparison of symptoms in the treatment group showed that there was no significant difference in the symptom scores of the adjacent weeks after taking Chinese medicine in the first 10 weeks(P>0.05),but there were significant differences in the symptom scores in the regions with large difference in weeks(P<0.05).In the treatment group,the percentage of complete withdrawal weeks was counted.It was found that the number of patients completed the withdrawal weeks started from the 10 weeks,and the number of patients was the largest.The percentage of patients who completed the withdrawal from the 12 weeks to the 18 weeks decreased gradually.LSD multiple comparison of PPI dose in the treatment group showed that the late PPI dose change was not statistically significant(P>0.05),but in the first 10 weeks,according to the symptom score every two weeks,the PPI dose of patients had significant statistical difference(P<0.05).By comparing the expression of gastrointestinal hormones before and after treatment,the treatment group can effectively improve the expression levels of GAS,VIP and MOT in GERD patients.The expression of VIP and mot in GERD patients was improved in the control group,but the expression level of gas was not statistically significant before and after treatment.After treatment,the treatment group could improve the secretion level of VIP and mot more effectively,but the improvement level of gas in the two groups was not statistically significant.By comparing the expression of inflammatory factors before and after treatment,the treatment group and the control group can effectively improve IL-6,IL-8,TNF-αin GERD patients;after treatment,the difference between the two groups was statistically significant.No side effects and adverse reactions were found in clinical application of Hezhong Jianpi Formula.Conclusion:Based on the clinical symptom observation table of gastroesophageal reflux disease,Hezhong Jianpi Formula can effectively improve the clinical symptoms of patients with dependence on proton pump inhibitors,and gradually reduce the dose of proton pump inhibitors.Hezhong Jianpi Formula can effectively improve the expression of gastrointestinal hormones VIP,MOT and inflammatory factors,which may be its potential mechanism,which is worthy of further exploration.No side effects and adverse reactions were found during the reduction treatment of Hezhong Jianpi Formula combined with proton pump inhibitor,so it has high safety and clinical practical value.