【目的】 探讨解郁化痰消瘀方对肝胃不和型胃癌前病变患者的临床疗效及其对核因子E2相关因子2（Nrf2）- Kelch样环 氧氯丙烷相关蛋白（Keap）信号通路的影响。【方法】 前瞻性选取 2023年 8月至 2024年 8月期间在天津市中医药研究院附属医 院脾胃病科接受治疗的100例肝胃不和型胃癌前病变患者为研究对象，使用随机数字表法将患者随机分为对照组和试验组， 每组各50例。对照组给予摩罗丹口服治疗，试验组给予解郁化痰消瘀方治疗，2组患者的疗程均为6个月。观察2组患者治 疗前后中医证候积分、胃镜病理积分和血清超氧化物歧化酶（SOD）、丙二醛（MDA）水平以及Nrf2-Keap信号通路相关基因和 蛋白表达水平的变化情况，并评价2组患者治疗6个月后的临床疗效。【结果】（1）临床疗效方面，治疗6个月后，试验组的总 有效率为 94.00%（47/50），对照组为 76.00%（38/50），组间比较（χ2检验），试验组的疗效明显优于对照组（P＜0.05）。（2）中医 证候积分方面，治疗后，2组患者的胃脘痛、胃胀、嗳气、纳差等中医证候积分均较治疗前降低（P＜0.05），且试验组的降 低幅度均明显优于对照组（P＜0.01）。（3）胃镜病理积分方面，治疗后，2组患者的胃黏膜萎缩、肠上皮化生、异型增生、慢 性炎症积分均较治疗前降低（P＜0.05），且试验组的降低幅度均明显优于对照组（P＜0.01）。（4）氧化应激指标方面，治疗后，2组患 者的血清SOD水平均较治疗前升高（P＜0.05），血清MDA水平均较治疗前降低（P＜0.05），且试验组对血清SOD水平的升高 幅度及对血清MDA水平的降低幅度均明显优于对照组（P＜0.05或P＜0.01）。（5）Nrf2-Keap信号通路相关基因表达水平方面， 治疗后，2组患者的胃黏膜组织Nrf2、醌氧化还原酶1（NQO1）、血红素加氧酶1（HO-1）基因mRNA相对表达水平均较治疗前 升高（P＜0.05），且试验组对胃黏膜组织 Nrf2、NQO1、HO-1 基因 mRNA 相对表达水平的升高幅度均明显优于对照组（P＜ 0.01）。（6）Nrf2-Keap信号通路相关蛋白表达水平方面，治疗后，2组患者的胃黏膜组织Nrf2、HO-1及线粒体超氧化物歧化酶 （SOD2）蛋白相对表达水平均较治疗前升高（P＜0.05），且试验组对胃黏膜组织Nrf2、HO-1、SOD2蛋白相对表达水平的升高 幅度均明显优于对照组（P＜0.01）。【结论】 解郁化痰消瘀方能有效改善肝胃不和型胃癌前病变患者的中医证候及胃镜病理表 现，提高血清抗氧化酶水平，上调Nrf2-Keap信号通路相关基因及蛋白表达，从而提高临床疗效，为胃癌前病变的治疗提供 了新的思路和方法。

Objective To investigate the clinical efficacy of Jieyu Huatan Xiaoyu Formula （JYHTXYF） in patients with gastric precancerous lesions （GPL） of liver-stomach disharmony type and to observe its effects on the nuclear factor erythroid 2-related factor 2（Nrf2）-Kelch-like ECH-associated protein 1（Keap1） signaling pathway. Methods A prospective study enrolled 100 GPL patients with liver-stomach disharmony syndrome treated at the Department of Gastroenterology，Affiliated Hospital of Tianjin Academy of Chinese Medicine from August 2023 to August 2024. Participants were randomized into control group （n=50，treated with Moluodan Pills） and trial group （n=50，treated with JYHTXYF decoction） for 6 months. Traditional Chinese medicine （TCM） syndrome scores， gastroscopic pathological scores，serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels，along with Nrf2-Keap pathway-related gene/protein expressions were assessed before and after treatment. Results （1） Regarding clinical efficacy，after 6 months of treatment，the total effective rate was 94.00% （47/50） in the trial group and 76.00% （38/50） in the control group. Intergroup comparison （by chi-square test） showed that the efficacy of the trial group was significantly superior to that of the control group （P＜0.05）.（2） In terms of traditional Chinese medicine （TCM） syndrome scores，after treatment，the scores for TCM syndromes such as epigastric pain，gastric distension，belching，and poor appetite decreased in both groups compared to those before treatment （P＜0.05）， and the reduction in the trial group was significantly superior to that in the control group （P＜0.01）.（3） Regarding gastroscopic pathological scores，after treatment，the scores for gastric mucosal atrophy，intestinal metaplasia， dysplasia， and chronic inflammation decreased in both groups compared to those before treatment （P＜0.05）， and the reduction in the trial group was significantly greater than that in the control group （P＜0.01）.（4） In terms of oxidative stress indicators，after treatment，SOD levels increased in both groups compared to before treatment （P＜0.05），while serum MDA levels decreased （P＜0.05）. The magnitude of increase in serum SOD levels and the magnitude of decrease in serum MDA levels in the trial group were significantly greater than those in the control group （P＜0.05 or P＜0.01）.（5） Regarding the expression levels of genes related to the Nrf2-Keap signaling pathway， after treatment， the relative mRNA expression levels of Nrf2， NAD（P）H quinone dehydrogenase 1 （NQO1），and heme oxygenase-1（HO-1） in gastric mucosal tissue increased in both groups compared to those before treatment （P＜0.05），and the increase in the trial group was significantly greater than that in the control group （P＜0.01）.（6） Regarding the expression levels of proteins related to the Nrf2-Keap signaling pathway，after treatment，the relative protein expression levels of Nrf2，HO-1，and mitochondrial superoxide dismutase （SOD2） in gastric mucosal tissue increased in both groups compared to those before treatment （P＜0.05），and the increase in the trial group was significantly greater than that in the control group （P＜0.01）. Conclusion JYHTXYF effectively improves TCM syndromes and gastroscopic pathology in GPL patients of liver-stomach disharmony type， elevates serum antioxidant enzyme levels，and upregulates the expression of genes and proteins associated with the Nrf2-Keap1 signaling pathway， thereby enhancing clinical efficacy. The study will provide novel insights and approaches for the treatment of gastric precancerous lesions.

R259.733

国家自然科学基金资助项目（编号：81802347）；天津市中医药重点领域科研项目（编号：2023004）