目的 建立小鼠醉酒模型，探究荆防颗粒的解酒作用及其作用机制。方法 将雌雄各半SPF级昆明种小鼠随机分为模型组和荆防颗粒组，模型组ig生理盐水，荆防颗粒组ig荆防颗粒30 min后，小鼠ig 56°红星二锅头（17 mL/kg）构建急性醉酒模型，以翻正反射消失/恢复时间评价各组小鼠醉酒潜伏期和睡眠时间，并计算醉酒率；转棒实验观察小鼠ig白酒10 min后的在棒时间，并观察小鼠胃黏膜损伤情况。进一步基于急性醉酒小鼠模型，观察药物对小鼠肝组织酒精代谢酶乙醇脱氢酶（alcohol dehydrogenase，ADH）、过氧化氢酶（catalyse，CAT）、细胞色素P450第二家族E亚型多肽1（cytochrome P4502E1，CYP2E1）、乙醛脱氢酶（acetaldehyde dehydrogenase，ALDH）的调节作用；Western blotting考察荆防颗粒对细胞自噬通路相关蛋白表达的影响。结果 与模型组比较，荆防颗粒降低小鼠醉酒率，并明显延长小鼠在棒时间及减轻胃黏膜损伤，表现出解酒作用；荆防颗粒显著提高模型小鼠肝组织ADH、CAT活力（P＜0.05、0.01、0.001），逆转过量饮酒导致的CYP2E1蛋白表达升高（P＜0.001），升高模型小鼠肝组织ADH1、ALDH2蛋白表达（P＜0.05、0.01）；明显上调模型小鼠肝组织微管相关蛋白1轻链3Ⅱ（microtubule-associated protein1 light chain 3Ⅱ，LC3Ⅱ）/LC3I值（P＜0.01），降低p62蛋白表达（P＜0.05）。结论 荆防颗粒能降低小鼠醉酒率，改善过度饮酒引起的中枢抑制及胃黏膜损伤表现，呈现出解酒作用；其作用机制可能与提高酒精代谢酶ADH、CAT、ALDH活力或表达以加速机体酒精代谢，激活自噬，缓解CYP2E1诱导的损伤有关。

Objective To investigate the anti-drinking effect and mechanism of Jingfang Granules (荆防颗粒) by establishing a mouse model of drunkenness. Methods Male and female half SPF grade Kunming mice were randomly divided into model group and Jingfang Granules group. After ig saline in model group and ig Jingfang Granules in Jingfang Granules group for 30 min, mice were ig liquor (17 mL/kg) to establish an acute intoxication model. The intoxication latency and sleep time of each group were evaluated by the disappearance/recovery time of righting reflex, and intoxication rate was calculated. The stick-turning experiment was conducted to observe the in-stick time of the mice after taking liquor for 10 min and to observe the damage to the gastric mucosa of the mice. Based on an acute intoxication mouse model, the effect of Jingfang Granules on alcohol metabolism enzymes such as alcohol dehydrogenase (ADH), catalase (CAT), cytochrome P450 second family E subtype polypeptide 1 (CYP2E1) and acetaldehyde dehydrogenase (ALDH) in liver tissue of mice were evaluated; Effect of Jingfang Granules on the expression of proteins related to the autophagy pathway were observed by Western blotting. Results Compared with model group, Jingfang Granules reduced the rate of intoxication and prolonged the time of mice on the stick, and alleviated the gastric mucosal damage, which showed the effect of an alcohol reliever; Jingfang Granules significantly increased ADH and CAT activity in liver tissues of model mice (P < 0.05, 0.01, 0.001), reversed the increase in CYP2E1 expression caused by excessive alcohol consumption (P < 0.001), and increased the expression of ADH1 and ALDH2 in liver tissue of model mice (P < 0.05, 0.01), significantly up-regulated the expression ratio of microtubule-associated protein1 light chain 3Ⅱ (LC3II)/LC3I in liver tissue (P < 0.01) and reduced the expression of p62 protein (P < 0.05). Conclusion Jingfang Granules could reduce the rate of intoxication in mice, and improve the manifestation of central inhibition and gastric mucosal damage caused by excessive alcohol consumption, which presents an antidotal effect. Its mechanism may be related to increasing the activity or expression of alcohol-metabolizing enzymes such as ADH, CAT and ALDH, which accelerate alcohol metabolism and activate autophagy to alleviate the CYP2E1-induced damage.

R285.5

国家自然科学基金资助项目（82074094）；西南特色中药资源国家重点实验室开放研究基金项目（2020XSGG002）