基于网络药理学探讨溪黄草治疗酒精性肝损伤的作用机制

刘文彬; 钟景斌; 王晖

doi:10.13386/j.issn1002-0306.2021080320

基于网络药理学探讨溪黄草治疗酒精性肝损伤的作用机制

Study on the Mechanism of Rabdosia serra in the Treatment of Alcoholic Liver Injury Based on Network Pharmacology

摘要

摘要: 目的：考察溪黄草对酒精性肝损伤的保护作用和潜在作用机制。方法：40只雌性昆明小鼠随机分为空白组、模型组、溪黄草组、阳性对照组。0.1 mL/10 g灌胃52°白酒建立酒精性肝损伤模型，连续给药10 d。末次给药，HE染色观察肝组织病理改变，试剂盒法测定血清指标。网络药理学方法分析溪黄草治疗酒精性肝损伤的潜在有效物质成分和信号通路、分子靶点，Western-blot验证相关分子靶点。结果：溪黄草组AST、m-AST、GDH蛋白表达水平显著高于模型组（P<0.05或P<0.01）；溪黄草组ADH和CAT蛋白水平表达显著高于模型组（P<0.05或P<0.01）；溪黄草组SOD和GSH-Px、GSH蛋白表达水平显著高于模型组（P<0.05或P<0.01），MDA蛋白表达水平显著低于模型组（P<0.05）；网络药理分析显示咖啡酸、迷迭香酸、槲皮素、胡麻素、异鼠李素是最可能的活性物质，Nrf2、CYP2E1、PTGS2、MMP9、MMP2是最可能的治疗靶点。Western-bolt验证结果显示经溪黄草给药干预后，溪黄草组与模型组相比，Nrf2蛋白表达极显著上调（P<0.01），CYP2E1蛋白表达极显著下调，具有统计学意义（P<0.01）。结论：溪黄草对酒精性肝损伤具有保护作用，其中机制可能与溪黄草降低CYP2E1水平，激活Nrf2的表达，从而降低氧化应激造成的损伤相关。

Abstract: Objective: To investigate the protective effect and potential mechanism of Rabdosia serra on alcoholic liver injury. Method: Forty female Kunming mice were randomly divided into blank group, model group, Rabdosia serra group and positive control group. All mice received 0.1 mL/10 g white spirit to established alcoholic liver injury model, and continuous administration for 10 days. After the last administration, HE staining was used to observe the pathological changes of liver tissue. Serum indexes were determined by kit method. Network pharmacology method was used to analyze the potential effective components, signal pathways and molecular targets of Rabdosia serra in the treatment of alcoholic liver injury, and Western blot was used to verify the related molecular targets. Results: The protein expression levels of AST, m-AST and GDH in Rabdosia serra group were significantly higher than those in model group (P<0.05 or P<0.01). The protein expression levels of ADH and CAT in Rabdosia serra group were significantly higher than those in model group (P<0.05 or P<0.01). The expression levels of SOD, GSH PX and GSH protein in Rabdosia serra group were significantly higher than those in model group (P<0.05 or P<0.01), and the expression level of MDA protein in the Rabdosia serra group was significantly lower than that in the model group (P<0.05). Network pharmacological analysis showed that caffeic acid, rosmarinic acid, quercetin, cannabinoid and isorhamnetin were the most likely active substances, and Nrf2, CYP2E1, PTGS2, MMP9 and MMP2 were the most likely therapeutic targets. Western bolt results showed that compared with the model group, the expression of Nrf2 protein in Rabdosia serra group was significantly up-regulated (P<0.01), and the expression of CYP2E1 protein was significantly down regulated (P<0.01). Conclusions: Rabdosia serra had protective effect on alcoholic liver injury, and the mechanism would be related to the decrease of CYP2E1 level, activation of Nrf2 expression, and reduction of oxidative stress damage.

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