黄藤素对CCl4致大鼠急性肝损伤的防治作用研究

Preventive and Therapeutic Effects of Berberine on Acute Liver Injury Induced by CCl4 in Rats

摘要: 目的：评价黄藤素(palmatine, Pal)对四氯化碳(CCl₄)诱导的大鼠急性肝损伤(ALI)的保护作用，初步探究其潜在靶点。方法：将48只大鼠随机分为正常对照组(NS)、模型组(CCl₄)、低剂量Pal组(Pal-L, 5 mg/kg)、中剂量Pal组(Pal-M, 10 mg/kg)、高剂量Pal组(Pal-H, 20 mg/kg)和地塞米松组(DEX, 10 mg/kg)腹腔注射5，10，20 mg/kg的Pal，每天一次，连续三天，NS组和CCl4组的大鼠腹腔注射给予等体积的生理盐水。Pal处理组的大鼠最后一次给药1小时后，CCl4组和Pal处理组的大鼠腹腔注射25%的CCl₄花生油溶液(3 ml/kg)，NS组的大鼠腹腔注射相同体积的溶剂。各组造模后开始计时，给予CCl₄ 24小时后处理所有大鼠，收集血清和肝组织，检测肺组织病理形态变化，评估肝损伤指标ALT和氧化应激指标MDA含量。网络药理学方法初步探究黄藤素抗急性肝损伤的潜在靶点。结果：Pal预处理剂量依赖性减轻CCl4诱导的急性肝损伤，表现为降低血清天冬氨酸转氨酶(AST)活性，抑制肝脏病理损伤。此外，Pal通过恢复丙二醛(MDA)水平来缓解CCl₄引发的氧化应激和炎症反应。结论：黄藤素能够通过抑制炎症反应和氧化应激发减轻急性肝损伤，STAT3可能是黄藤素发挥肝脏保护作用最具潜力的靶点。

Abstract: Objective: To evaluate the protective effect of palmatine (Pal) against carbon tetrachloride (CCl₄)-induced acute liver injury (ALI) in rats, and preliminarily explore the potential targets of palmatine. Methods: 48 rats were randomly divided into a normal control group (NS), a model group (CCl₄), a low dose Pal group (Pal-L, 5 mg/kg), a medium dose Pal group (Pal-M, 10 mg/kg), a high dose Pal group (Pal-H, 20 mg/kg), and a dexamethasone group (DEX, 10 mg/kg). Rats in the NS and CCl₄ groups were intraperitoneally injected with 5, 10, and 20 mg/kg of Pal once a day for three consecutive days. Rats in the NS and CCl4 groups were given equal volumes of physiological saline by intraperitoneal injection. After the last administration of 1 hour, rats in the Pal-treated groups were intraperitoneally injected with 25% CCl4 peanut oil solution (3 ml/kg), while rats in the NS group were intraperitoneally injected with the same volume of solvent. After modeling, each group began timing, and all rats were treated with CCl₄ 24 hours later. Serum and liver tissue were collected to observe the pathological and morphological changes in lung tissue and evaluate the liver injury index ALT and oxidative stress index MDA content. Network pharmacology methods were used to preliminarily explore the potential targets of palmatine in treating acute liver injury. Results: Pal pretreatment attenuated CCl₄-induced acute liver injury in a dose-dependent manner, manifested by a decrease in serum aspartate aminotransferase (AST) activity and inhibition of liver pathological damage. In addition, Pal alleviates oxidative stress and inflammatory responses induced by CCl₄ by restoring malondialdehyde (MDA) levels. Conclusion: Palmatine can alleviate acute liver injury by inhibiting inflammatory reactions and oxidative stress. STAT3 may be the most potential target for Palmatine to exert liver protective effects.