目的 探讨胃衡汤调控核因子E2相关因子2(Nrf2)-Kelch样环氧氯丙烷相关蛋白(Keap)信号通路抑制老年胃癌前病变(Precancerous lesions of gastric cancer,PLGC)患者氧化应激反应的作用.方法 选取2022年3月-2023年3月期间于南京中医药大学第二附属医院消化腔镜中心和脾胃病科就诊的PLGC老年患者60例,按随机数字表法分为基础治疗组与胃衡汤治疗组,每组各30例.另选择同期常规胃镜体检的慢性浅表性胃炎患者30例为对照组.对照组仅入组接受研究相关指标检测,不予治疗.基础治疗组患者给予雷贝拉唑钠肠溶胶囊,胃衡汤组在基础治疗组上加用胃衡汤治疗,均治疗6个月.观察比较两组PLGC患者临床疗效、安全性,治疗前后中医证候评分、胃镜病理分级及Nrf2-Keap通路相关蛋白检测.结果 治疗后胃衡汤治疗组中医证候疗效总有效率93.33％(28/30)明显高于基础治疗组76.67％(23/30),差异有统计学意义(P＜0.05).治疗后胃衡汤治疗组病理组织学疗效总有效率83.33％(25/30)明显高于基础治疗组63.33％(19/30),差异有统计学意义(P＜0.05).治疗后两组患者中医证候各项积分及总积分均较治疗前降低,差异有统计学意义(P＜0.05);且胃衡汤治疗组中医证候各项积分及总积分均明显低于基础治疗组,差异有统计学意义(P＜0.05).治疗后两组患者胃黏膜组织学各项积分及总分均较治疗前降低,差异有统计学意义(P＜0.05);且胃衡汤治疗组胃黏膜组织学各项积分及总分均明显低于基础治疗组,差异有统计学意义(P＜0.05).治疗后两组患者Nrf2和SOD表达高于治疗前,Keap1和MDA表达较治疗前降低,差异有统计学意义(P＜0.05);且胃衡汤治疗组Nrf2和SOD表达明显高于基础治疗组,Keap1和MDA表达明显低于基础治疗组,差异有统计学意义(P＜0.05).治疗期间,两组患者治疗前后肝肾功能、三大常规及心电图检查均未发现异常.结论 胃衡汤治疗老年PLGC能够改善临床症状,抑制甚至逆转病理学改变,提高治疗效果,其机制与调节Nrf2-Keap信号通路而抑制氧化应激反应有关.
Clinical Study on Weiheng Decoction in Regulating the Nrf2-Keap Signal Pathway to Inhibit Oxidative Stress in Elderly Patients with Precancerous Lesions of Gastric Cancer
Objective To investigate the effect of Weiheng decoction in regulating nuclear factor E2-related fac-tor 2(Nrf2)-Kelch-like ECH-associated protein(Keap)signal pathway to inhibit oxidative stress response in elderly patients with precancerous lesions of gastric cancer(PLGC).Methods From March 2022 to March 2023,60 elderly pa-tients with PLGC who visited the Gastrointestinal Endoscopic Treatment Center and the Department of Spleen and Gastroen-terology at the Second Affiliated Hospital of Nanjing University of Chinese Medicine were selected as the research subjects.They were divided into a basic treatment group and a Weiheng decoction treatment group by the random number table method,with 30 patients in each group.Additionally,30 patients with chronic superficial gastritis undergoing routine gastro-scopic examination during the same period were selected as the control group.The control group only participated in study-related indicator tests without receiving treatment.The basic treatment group was treated with rabeprazole sodium enteric-coated capsules,while the Weiheng decoction treatment group was treated with Weiheng decoction in addition to the basic treatment group,both for 6 months.The clinical efficacy,safety,traditional Chinese medicine(TCM)syndrome scores,gas-troscopy pathological grading,and Nrf2-Keap pathway-related protein levels were observed and compared before and af-ter treatment in PLGC patients between the two groups.Results The total effective rate of TCM symptom efficacy in the Weiheng decoction treatment group was 93.33％(28/30),significantly higher than the 76.67％(23/30)in the basic treat-ment group,with a statistically significant difference(P＜0.05).The total effective rate of histological efficacy in the Weiheng decoction treatment group was 83.33％(25/30),significantly higher than 63.33％(19/30)in the basic treat-ment group,with a statistically significant difference(P＜0.05).After treatment,the scores of TCM symptoms and total scores in both groups decreased significantly compared to before treatment,with a statistically significant difference(P＜0.05).Moreover,the scores of TCM symptoms and total scores in the Weiheng decoction treatment group were significantly lower than those in the basic treatment group,with a statistically significant difference(P＜0.05).After treatment,gastric mucosal histology scores and total scores in both groups decreased significantly compared to before treatment,with a statis-tically significant difference(P＜0.05).Additionally,gastric mucosal histology scores and total scores in the Weiheng de-coction treatment group were significantly lower than those in the basic treatment group,with a statistically significant difference(P＜0.05).After treatment,the expression of Nrf2 and SOD in both groups was higher than before treatment,and the expression of Keap1 and MDA was lower than before treatment,with a statistically significant difference(P＜0.05).Furthermore,the expression of Nrf2 and SOD in the Weiheng decoction treatment group was significantly higher than in the basic treatment group,and the expression of Keap1 and MDA was significantly lower than in the basic treatment group,with a statistically significant difference(P＜0.05).During the treatment period,no abnormalities were found in liv-er and kidney function,routine blood tests,and electrocardiograms in either group.Conclusion Weiheng decoction can improve clinical symptoms,inhibit or even reverse pathological changes,and enhance the therapeutic effect in elderly PLGC patients.Its mechanism is related to the regulation of the Nrf2-Keap signal pathway and the inhibition of oxidative stress.
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