【目的】观察乌梅丸对糖尿病胃轻瘫（DGP）小鼠的治疗作用及配伍机制。【方法】将69只C57BL/6J小鼠随机分为正常组（12只）和造模组（57只）。采用60%高脂饲料喂养结合腹腔注射链脲佐菌素（STZ）法将造模组小鼠构建成DGP模型。成功建模后，将造模组小鼠随机分为模型组、乌梅丸全方组、乌梅丸酸味药组、乌梅丸苦味药组、乌梅丸甘味药组和乌梅丸辛味药组，每组9只。经过28d治疗后，测定小鼠胃排空率、小肠推进率，采用苏木素-伊红（HE）染色观察胃窦病理变化，应用血糖仪检测小鼠空腹血糖（FBS），采用比色法检测甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平，采用酶联免疫吸附分析（ELISA）法检测胃窦组织胃泌素（GAS）、胃动素（MTL）、血管活性肠肽（VIP）含量，采用Western Blot法检测胃窦组织中Kelch样ECH关联蛋白1（Keap-1）、核因子红细胞系2相关因子2（Nrf-2）、NAD（P）H：醌氧化还原酶1（Nqo-1）、超氧化物歧化酶1（Sod-1）蛋白表达量。【结果】（1）与正常组比较，模型组小鼠血清FBS、TG、TC和LDL-C水平显著升高（P＜0.05或P＜0.01或P＜0.001）；与模型组比较，乌梅丸全方组、酸味药组和苦味药组第3、4周末血糖值显著下降（P＜0.05或P＜0.01或P＜0.001），乌梅丸全方组血清TG、TC、LDL-C水平显著降低（P＜0.05或P＜0.01），乌梅丸酸味药组、苦味药组、甘味药组及辛味药组血清TC水平均显著下降（P＜0.05），拆方组中仅乌梅丸酸味药组LDL-C水平显著下降（P＜0.05）。（2）与正常组比较，模型组小鼠胃窦黏膜层及黏膜下层腺体细胞排列紊乱；与模型组比较，乌梅丸全方组胃窦组织病理损伤得到明显改善，酸味药组、苦味药组DGP小鼠胃窦组织损伤的恢复效果优于甘味药组和辛味药组。（3）与正常组比较，模型组小鼠胃排空率和小肠推进率降低（P＜0.01或P＜0.001）；与模型组比较，乌梅丸全方组、酸味药组及苦味药组胃排空率均显著升高（P＜0.05或P＜0.001），乌梅丸全方组、酸味药组、苦味药组、甘味药组、辛味药组小肠推进率均显著升高（P＜0.05或P＜0.01或P＜0.001）。（4）与正常组比较，模型组小鼠胃窦组织VIP含量显著升高（P＜0.01），GAS、MTL含量显著降低（P＜0.01或P＜0.001）；与模型组比较，乌梅丸全方组、酸味药组、苦味药组、甘味药组GAS含量均显著升高（P＜0.01或P＜0.001），乌梅丸全方组、苦味药组小鼠MTL含量显著升高（P＜0.05或P＜0.01），乌梅丸全方组、酸味药组、苦味药组、甘味药组小鼠胃窦组织VIP含量均显著降低（P＜0.05或P＜0.01或P＜0.001）。（5）与正常组比较，模型组小鼠胃窦组织Keap-1表达水平升高（P＜0.05），Nrf-2、Nqo-1和Sod-1表达水平降低（P＜0.05或P＜0.001）；与模型组比较，乌梅丸全方组及苦味药组Keap-1蛋白表达水平显著降低（P＜0.05或P＜0.001），乌梅丸全方组、酸味药组及苦味药组Nrf-2、Nqo-1、Sod-1表达水平显著升高（P＜0.05或P＜0.001）。【结论】乌梅丸可有效调节DGP小鼠糖脂代谢、改善胃窦损伤、促进胃肠动力，全方药效优于各拆方，其机制可能与酸味药、苦味药、甘味药、辛味药协同配伍增效，且主要通过酸味药和苦味药调节Nrf-2/Keap-1通路进而改善氧化应激损伤有关。

Objective To observe the therapeutic effect and compatibility mechanism of Wumei Wan on diabetic gastroparesis（DGP）mice. Methods Sixty-nine C57BL/6J mice were randomly divided into normal group（12 mice）and model group（57 mice）. The DGP model was constructed by 60% high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）. After successful modeling，the mice in the model group were randomly divided into model group，Wumei Wan whole prescription group，Wumei Wan sour medicine group，Wumei Wan bitter medicine group，Wumei Wan sweet medicine group and Wumei Wan pungent medicine group，with nine mice in each group. After 28 days of treatment，the gastric emptying rate and small intestinal propulsion rate of mice were measured. The pathological changes of gastric antrum were observed by hematoxylin-eosin（HE）staining. The fasting blood glucose（FBS）of mice was detected by blood glucose meter. The levels of triglyceride（TG），total cholesterol（TC）and low density lipoprotein cholesterol（LDL-C）were detected by colorimetry. The contents of gastrin （GAS）， motilin （MTL）and vasoactive intestinal peptide（VIP）in gastric antrum were detected by enzyme-linked immunosorbent assay（ELISA）. Western Blot was used to detect the expression of Kelch-like ECH-associated protein 1（Keap-1），nuclear factor erythroid 2-related factor 2（Nrf-2），NAD（P） H：quinone oxidoreductase 1（Nqo-1）and superoxide dismutase 1（Sod-1）in gastric antrum tissue. Results （1）Compared with the normal group，the levels of serum FBS，TG，TC and LDL-C in the model group were significantly increased（P＜0.05 or P＜0.01 or P＜0.001）；compared with the model group，the blood glucose level of the whole prescription group，the sour medicine group and the bitter medicine group was decreased significantly at the end of the third and fourth week（P＜0.05 or P＜0.01 or P＜0.001），the serum TG，TC and LDL-C levels of the whole prescription group were significantly decreased（P＜0.05 or P＜0.01），the serum TC level of the sour medicine group， the bitter medicine group，the sweet medicine group and the pungent medicine group was significantly decreased（P＜0.05），and only the LDL-C level of the sour medicine group was significantly decreased（P＜0.05）.（2）Compared with the normal group，the glandular cells in the gastric antrum mucosa and submucosa of the model group were disordered；compared with the model group，the pathological damage of gastric antrum tissue in Wumei Wan whole prescription group was significantly improved，the recovery effect of gastric antrum tissue damage in DGP mice in the sour medicine group and the bitter medicine group was superior to that in the sweet medicine group and the pungent medicine group.（3）Compared with the normal group，the gastric emptying rate and small intestinal propulsion rate of the model group were decreased （P＜0.01 or P＜0.001）；compared with the model group，the gastric emptying rate of the whole prescription group，the sour medicine group and the bitter medicine group was significantly increased （P＜0.05 or P＜0.001）， and the intestinal propulsion rate of the whole prescription group，the sour medicine group，the bitter medicine group，the sweet medicine group and the pungent medicine group was significantly increased（P＜0.05 or P＜0.01 or P＜0.001）. （4）Compared with the normal group，the content of VIP in the gastric antrum tissue of the model group was significantly increased（P＜0.01），and the contents of GAS and MTL were significantly decreased（P＜0.01 or P＜0.001）. Compared with the model group，the content of GAS in Wumei Wan whole prescription group，the sour medicine group，the bitter medicine group and the sweet medicine group was significantly increased（P＜0.01 or P＜0.001），the content of MTL in the whole prescription group and the bitter medicine group was significantly increased （P＜0.05 or P＜0.01），and the content of VIP in gastric antrum tissue of mice in Wumei Wan whole prescription group，sour medicine group，bitter medicine group and sweet medicine group was significantly decreased（P＜0.05 or P＜0.01 or P＜0.001）.（5）Compared with the normal group，the expression level of Keap-1 in the gastric antrum tissue of the model group was increased（P＜0.05），and the expressions of Nrf-2，Nqo-1 and Sod-1 were decreased（P＜0.05 or P＜0.001）. Compared with the model group，the expression level of Keap-1 protein in the whole prescription group and the bitter medicine group was significantly decreased（P＜0.05 or P＜0.001），and the expression levels of Nrf-2，Nqo-1 and Sod-1 in the whole prescription group，the sour medicine group and the bitter medicine group were significantly increased（P＜0.05 or P＜0.001）. Conclusion Wumei Wan can effectively regulate glucose and lipid metabolism，improve gastric antrum injury and promote gastrointestinal motility in DGP mice. The efficacy of the whole prescription is superior to that of each disassembled prescription. The mechanism may be related to the synergistic compatibility of sour medicine，bitter medicine，sweet medicine and pungent medicine，and mainly through sour medicine and bitter medicine regulating Nrf-2/Keap-1 pathway further to improve oxidative stress injury.

R285.5

广东省自然科学基金资助课题 （编号：2023A1515010843）；广东省普通高校重点领域专项 （编号：2023ZDZX2018）