【目的】探讨健胃消胀片对大鼠胃癌前病变的治疗作用及机制。【方法】将40只雄性SD大鼠随机分为正常组、模型组、 叶酸组和健胃消胀片组，每组10只。除正常组，其他3组大鼠采用雷尼替丁水溶液灌胃联合N-甲基-N’-硝基-N-亚硝基胍 （MNNG）溶液饮用法制备胃癌前病变模型。成功造模后，相应给药治疗7周。记录造模及给药期间大鼠体质量变化，观察胃 部大体观并进行病理评分，测定脾脏、肝脏系数，采用苏木素-伊红（HE）染色法观察胃组织病理形态变化，酶联免疫吸附分 析（ELISA）检测血清胃泌素（GAS）、胃动素（MTL）、胰高血糖素（GC）含量，阿利新蓝-过碘酸雪夫氏（AB-PAS）染色法观察胃 组织黏膜层厚度，蛋白免疫印迹（Western Blot）法检测胃组织磷脂酰肌醇3-激酶（PI3K）、磷酸化PI3K（p-PI3K）、蛋白激酶B （Akt）、磷酸化Akt（p-Akt）、内皮型一氧化氮合酶（eNOS）蛋白的表达，免疫荧光染色法检测胃组织血管内皮细胞生长因子A （VEGFA）蛋白的表达。【结果】与正常组比较，模型组大鼠实验期间体质量增长慢，胃部大体观病理评分显著升高（P＜ 0.01），脾脏系数和肝脏系数显著降低（P＜0.01），胃组织出现杯状细胞增生、肠化生现象，胃组织炎症评分显著升高（P＜ 0.01），血清GAS 含量显著升高（P＜0.01），MTL、GC 含量显著降低（P＜0.05），胃组织黏膜层厚度显著减小（P＜0.05）， PI3K、p-PI3K、Akt、p-Akt、eNOS蛋白表达水平降低（P＜0.01），VEGFA蛋白表达水平降低（P＜0.01）；与模型组比较，健 胃消胀片组和叶酸组上述指标均得到明显改善（P＜0.05或P＜0.01），其中，在胃组织杯状细胞增生、肠化生现象，血清GAS 含量，胃组织黏膜层厚度方面，健胃消胀片组改善效果更优。【结论】健胃消胀片可改善大鼠胃癌前病变，其机制可能与激 活PI3K-Akt-eNOS通路进而促进胃损伤组织的血管生成和修复能力有关。

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer（PLGC）. Methods Forty male SD rats were randomly divided into the normal group，the model group，the folic acid group and the Jianwei Xiaozhang Tablets group，with 10 rats in each group. In addition to the normal group，the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N’-nitro-N-nitrosoguanidine（MNNG）solution drinking method for the preparation of PLGC model. After successful modeling，drugs were administered accordingly for 7 weeks. The 广州中医药大学学报 Journal of Guangzhou University of Traditional Chinese Medicine 2024年3月第41卷第3期 March 2024，Vol. 41，No. 3 709 changes in body mass of rats during modeling and drug administration were recorded，the gross view of the stomach was observed and scored pathologically， the coefficients of spleen and liver were determined， the pathological changes in gastric tissue were observed by hematoxylin-eosin（HE）staining，enzyme-linked immunosorbent assay （ELISA）was used to measure serum gastrin（GAS），motilin（MTL）and glucagon（GC），Alisin Blue-Periodic Acid Schiff’s（AB-PAS）staining was used to observe the thickness of the mucosal layer of gastric tissues，the expressions of phosphatidylinositol 3-kinase（PI3K），phosphorylated PI3K（p-PI3K），protein kinase B（Akt）， phosphorylated Akt（p-Akt），and endothelial-type nitric oxide synthase（eNOS）proteins in gastric tissues were detected by protein immunoblotting（Western Blot）， and the expression of vascular endothelial growth factor A （VEGFA）protein in gastric tissues was detected by immunofluorescence staining. Results Compared with the normal group， the body mass of rats in the model group grew slowly during the experimental period， gastric macroscopic pathological scores were significantly increased （P＜0.01）， splenic coefficient and hepatic coefficient were significantly decreased（P＜0.01），the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis，gastric tissues’inflammation scores were significantly increased（P＜0.01），the serum GAS content was significantly increased（P＜0.01），and the MTL，GC contents were significantly reduced（P＜0.05），and the thickness of the mucous membrane layer of gastric tissue was significantly reduced（P＜0.05）， the protein expression levels of PI3K，p-PI3K，Akt，p-Akt and eNOS were reduced（P＜0.01），and the protein expression level of VEGFA was reduced（P＜0.01）； compared with the model group， the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved（P＜0.05 or P＜0.01），among which，the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues， the content of serum GAS， and the thickness of the mucous layer in gastric tissues. Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway，which in turn promotes the angiogenesis and repair of gastric damaged tissues.

R285.5

国家自然科学基金资助项目（编号：82274381）；广东省基础与应用基础粤莞联合基金资助项目（编号：2022A1515140124）；广东省 基础与应用基础粤企联合基金资助项目（编号：2022A1515220059）；广东省中医药局科研项目（编号：20231368）