健脾醒酒方通过雌激素受体1调控PI3K/Akt通路改善酒精诱导的肝细胞损伤*

作者：李 堃1，周广泉1，杨 琰1，葛 飞2

单位：1.海安市中医院，江苏 海安 226000； 2.无锡市第二人民医院，江苏 无锡 214043

引用：引用：李堃，周广泉，杨琰，葛飞.健脾醒酒方通过雌激素受体1调控PI3K/Akt通路改善酒精诱导的肝细胞损伤[J].中医药导报,2025,31(9):44-49.

DOI：10.13862/j.cn43-1446/r.2025.09.007

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摘要：目的：研究健脾醒酒方通过雌激素受体1（ESR1）对磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）通路的调控作用，以明确其对酒精诱导肝细胞损伤小鼠的影响及其作用机制。方法:将60只SPF级BALB/c雄性小鼠适应性饲养1周后随机分为空白组、模型组、健脾醒酒方低剂量组、健脾醒酒方高剂量组、阳性药组1和阳性药组2，每组10只。除空白组外各组喂养含乙醇去离子水，从第2天至第5天乙醇体积分数分别从1%逐渐增加至4%，第6天至第13天为5%，第7天开始灌胃0.5 mL 20%乙醇，非酒精喂养组接受等体积去离子水，第8天开始各组小鼠灌胃相应药物7 d，空白组及模型组灌胃等体积去离子水。末次灌胃后0.5 h，摘眼球取血，处死小鼠解剖取肝脏和胃。采用气相色谱法测定乙醇含量；赖氏法检测各组小鼠谷丙转氨酶（ALT）、谷草转氨酶（AST）；比色法检测乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）水平；ELISA法检测超氧化物歧化酶（SOD）、丙二醛（MDA）、白细胞介素6（IL-6)、肿瘤坏死因子-α（TNF-α)；Western blotting法检测小鼠肝脏组织中PI3K、Akt、p-PI3K、p-Akt、ESR1、基质金属蛋白酶-2（MMP-2）表达水平及胃组织中PTPN11表达水平；光学显微镜观察小鼠肝胃组织病理切片。结果:健脾醒酒方低剂量组、健脾醒酒方高剂量组、阳性药组1小鼠血液乙醇含量均低于模型组（P<0.05）；与模型组小鼠比较，健脾醒酒方低剂量组、健脾醒酒方高剂量组、阳性药组1小鼠的ADH、ALDH均升高，ALT、AST均降低（P<0.05）；与模型组小鼠相比，健脾醒酒方低剂量组、健脾醒酒方高剂量组、阳性药组1、阳性药组2的IL-6、TNF-α、MDA均降低，SOD均升高（P<0.05）；与模型组小鼠相比，健脾醒酒方低剂量组、健脾醒酒方高剂量组ESR1、MMP-2、PTPN11、p-PI3K/PI3K、p-Akt/Akt蛋白表达均降低（P<0.05）；肝胃组织病理形态学显示健脾醒酒方高剂量组病理情况明显改善。结论:健脾醒酒方可能通过ESR1调控的PI3K/Akt信号通路，抑制MMP-2、PTPN11蛋白表达，从而降低血液乙醇含量，减轻酒精诱导的肝脏、胃黏膜炎症损伤，缓解轻度酒精中毒。

关键词：酒精性肝损伤；健脾醒酒方；雌激素受体1；磷脂酰肌醇3-激酶/蛋白激酶B信号通路；小鼠

Abstract：

Objective: To study the regulation of Jianpi Xingjiu recipe through estrogen receptor 1 (ESR1) by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway to explore its effect on alcohol-induced liver cell injury in mice and its mechanism of action. Methods: Totally 60 SPF grade BALB/c male mice were adaptively raised for 1 week and randomly divided into blank group, model group, Jianpi Xingjiu recipe low-dose group, Jianpi Xingjiu recipe high-dose group, positive drug group 1 and positive drug group 2, 10 rats in each group. Except for the blank group, each group was fed deionized water containing ethanol. From the 2nd to the 5th day, the ethanol concentration gradually increased from 1% to 4%, and from the 6th to the 13th day, the ethanol concentration was 5%. Starting from the 7th day, 0.5 mL of 20% ethanol was administered by intragastric administration, and the non-alcohol feeding group received an equal volume of deionized water. Starting from the 8th day, the mice in each group were administered with corresponding drugs for 7 days, and the blank group and model group were administered with an equal volume of deionized water. The eyeballs were removed to collect blood 0.5 h after the last gastric administration. The mice were sacrificed and the liver and stomach were dissected and removed. Gas chromatography was used to determine ethanol content, and Reich's method was used to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Colorimetric method was used to detect alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) levels. Enzyme-linked immunosorbent assay (ELISA) method was used to detect superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Western blotting method was used to detect the expression levels of PI3K, Akt, p-PI3K, p-Akt, ESR1 and MMP-2 in liver tissue and the expression level of PTPN11 in gastric tissue. The pathological sections of mouse liver and stomach tissue were observed with an optical microscope. Results: The Jianpi Xingjiu recipe low-dose group, Jianpi Xingjiu recipe high-dose group and positive drug group 1 showed lower blood ethanol contents than model group (P<0.05). Compared with the model group, ADH and ALDH increased in Jianpi Xingjiu recipe low-dose group, Jianpi Xingjiu recipe high-dose group and positive drug group 1, while ALT and AST decreased (P<0.05). Compared with the model group, the IL-6, TNF-α and MDA decreased in Jianpi Xingjiu recipe low-dose group, Jianpi Xingjiu recipe high-dose group, positive drug group 1 and positive drug group 2, while SOD increased (P<0.05). Compared with the model group, the protein expressions of ESR1, MMP-2, PTPN11, p-PI3K/PI3K, and p-Akt/Akt were reduced in Jianpi Xingjiu recipe low-dose group and Jianpi Xingjiu recipe high-dose group (P<0.05), and liver and stomach tissue pathological morphology showed that the pathological conditions were significantly improved in Jianpi Xingjiu recipe high-dose group. Conclusion： Jianpi Xingjiu recipe may inhibit MMP-2 and PTPN11 protein expression through the PI3K/Akt signaling pathway regulated by ESR1, thereby reducing blood ethanol content, alleviating alcohol-induced liver and gastric mucosal inflammatory damage, and alleviating mild alcoholism.

Key words：alcoholic liver injury; Jianpi Xingjiu recipe; estrogen receptor1; phosphatidylinositol 3-kinase/protein kinase B pathway; mice

发布时间：2026-01-08

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