目的 研究四君子汤对乙醇诱导的小鼠急性胃肠黏膜损伤的保护作用。方法 将60只小鼠随机分为6组：对照组、模型组、奥美拉唑（阳性药，4 mg·kg^-1）组和四君子汤低、中、高剂量（4、6、8 g·kg^-1）组，每组10只，连续ig给药14 d后，在造模前全部小鼠禁食禁水24 h，末次给药1 h后，除对照组外，其余各组小鼠每只ig无水乙醇10 mL·kg^-1诱发急性胃肠黏膜损伤。造模1 h后，脱颈椎处死小鼠后开腹，取出胃及十二指肠，观察胃黏膜的损伤情况并拍照，分析小鼠胃黏膜损伤分数、治疗指数；HE染色观察胃及十二指肠黏膜病理组织学变化；试剂盒法检测血清丙二醛（MDA）、总超氧化物歧化酶（SOD）水平； Westernblotting法检测胃肠组织白细胞介素-1β （IL-1β）、白细胞介素-10 （IL-10）和肿瘤坏死因子-α （TNF-α）蛋白表达水平。结果 胃黏膜损伤评价结果显示，与对照组比较，模型组小鼠胃黏膜有明显出血带；与模型组比较，各用药组小鼠胃黏膜损伤有不同程度的改善，损伤分数均显著降低（P＜0.05、0.001） ，四君子汤高剂量组治疗效果最好，治疗指数达到72.54%，与阳性药奥美拉唑治疗效果相当。HE染色结果显示，模型组小鼠胃及十二指肠腺体排列紊乱，黏膜上皮细胞大量坏死、脱落，四君子汤发挥明显改善作用。与模型组比较，四君子汤中、高剂量组以及奥美拉唑组小鼠血清中MDA水平显著下降（P＜0.001）、SOD活性显著升高（P＜0.05、0.001），胃及十二指肠组织IL-1β、TNF-α蛋白表达显著下降（P＜0.05、0.01、0.001），IL-10蛋白表达显著增加（P＜0.01）。结论 四君子汤可能通过抑制炎症和抗氧化应激反应对乙醇诱导的小鼠急性胃肠黏膜损伤发挥保护作用。

Objective To study the protective effect of Sijunzi Decoction on acute gastrointestinal mucosal injury induced by ethanol in mice. Methods Sixty Kunming mice were randomly divided into control group, model group, omeprazole (positive drug, 4 mg·kg^-1) group, Sijunzi Decoction low, medium, high dose group (4, 6, and 8 g·kg^-1), with 10 mice in each group. After 14 days of continuous ig administration, all mice were fasting and water abstention for 24 h before modeling. After 1 h of last administration, except the control group, other mice in each group were given anhydrous ethanol of 10 mL·kg^-1 ig to induce acute gastrointestinal mucosal injury. One hour after the model was made, the mice were killed by cervical spondylosis, and then the stomach and duodenum were taken out. The injury of gastric mucosa was observed and photographed, and the injury score and treatment index of gastric mucosa were analyzed. HE staining was used to observe the histopathological changes of gastric and duodenal mucosa. The serum levels of malondialdehyde (MDA) and total superoxide dismutase (SOD) were detected by the kit method. Detection of interleukin-1β (IL-1β), Interleukin-10 (IL-10) and tumor necrosis factor- α (TNF-α) protein expression level in gastrointestinal tissue by Western blotting. Results The evaluation results of gastric mucosal injury showed that, compared with control group, the mice in the model group had obvious bleeding bands in the gastric mucosa. Compared with the model group, the gastric mucosal injury of mice in each drug group was improved to different degrees, and the injury score was significantly reduced (P< 0.05, 0.001), and the high dose group had the best treatment effect with a treatment index of 72.54%, which was comparable to the treatment effect of the positive drug omeprazole. HE staining results show that, the arrangement of gastric and duodenal glands in the model group of mice was disordered, and the mucosal epithelial cells were necrotic and detached in large numbers. Sijunzi Decoction could improve the anhydrous ethanol-induced gastrointestinal mucosal injury in mice. Compared with model group, the level of MDA in serum of mice in the middle and high dose groups of Sijunzi Decoction and omeprazole groups decreased significantly (P< 0.001), the activity of SOD increased significantly (P< 0.05、0.001), and the protein expression level of IL-1β and TNF-α in gastric and duodenal tissues decreased significantly (P< 0.05、0.01、0.001), and the expression of IL-10 protein increased significantly (P< 0.01). Conclusion Sijunzi Decoction has protective effect on ethanol-induced acute gastrointestinal mucosal injury in mice by inhibiting inflammatory response and anti-oxidative stress response.

R285.5

安徽省高校自然科学研究项目（KJ2019A0226）；2020年安徽省大学生创新创业训练计划项目（S202010366003）