目的 研究丹参酮IIA(tanshinone ⅡA, Tan ⅡA)对CCl4诱导小鼠急性肝损伤的抗氧化、保护作用及其可能的作用机制。 方法 将C57BL/6J小鼠随机分成正常组、CCl4组以及Tan ⅡA保护组(Tan ⅡA 20 mg/kg+CCl4)，每组10只。腹腔注射CCl4构建小鼠急性肝损伤模型。计算各组小鼠的肝脏指数，检测血清AST和ALT活性，测定肝组织SOD活性及GSH、MDA含量，HE染色观察肝组织病理变化，免疫组织化学法和Western blot检测肝组织PI3K、p-PI3K、Akt、p-Akt、Nrf2和HO-1蛋白表达水平。 结果 与CCl4组相比，Tan ⅡA保护组肝脏指数显著下降(P<0.01)，血清AST(P<0.01)和ALT活性降低(P<0.05)，肝组织SOD活性(P<0.01)及GSH含量升高(P<0.05)，MDA含量降低(P<0.05)，肝组织病理变化得到显著改善。同时，Tan ⅡA使肝组织p-PI3K和p-Akt表达水平明显升高(P<0.01)，显著诱导Nrf2转位入核(P<0.01)，促使其下游靶蛋白HO-1表达水平明显升高(P<0.01)。 结论 Tan ⅡA能够显著改善CCl4诱导的急性肝损伤，其机制可能与PI3K/Akt/Nrf2/HO-1信号通路有关。
Abstract
Objective To investigate the antioxidant and protective effect of tanshinone IIA (Tan ⅡA) on CCl4-induced acute liver injury in mice and its possible mechanism. Methods C57BL/6J mice were randomly divided into a control group, a CCl4 group and a Tan ⅡA protective group (Tan ⅡA 20 mg/kg+CCl4), with 10 mice in each group. Acute liver injury model was induced by intraperitoneal injection of CCl4 in mice. The liver indices were calculated, the activities of serum AST and ALT were detected, the activity of SOD and the contents of GSH and MDA in liver tissue were measured, and the pathological changes of liver tissue were observed by HE staining. The expression levels of PI3K, p-PI3K, Akt, p-Akt, Nrf2 and HO-1 proteins in liver tissue were detected by immunohistochemistry and Western blot. Results Compared with the CCl4 group, in the Tan ⅡA protective group, the liver indices was significantly decreased (P<0.01), the activities of serum AST (P<0.01) and ALT (P<0.05) was reduced, the activity of SOD (P<0.01) and the content of GSH (P<0.05) were increased while decreasing the content of MDA (P<0.05) in liver tissue, and the pathological changes of liver tissue was significantly improved. In addition, Tan ⅡA could significantly increase the expression levels of p-PI3K and p-Akt (P<0.01) in liver tissue, while significantly inducing Nrf2 translocation into nucleus (P<0.01), which significantly increased the expression level of its downstream target protein HO-1 (P<0.01). Conclusions Tan ⅡA can significantly ameliorate CCl4-induced acute liver injury. Its mechanism may be related to PI3K/Akt/Nrf2/HO-1 signaling pathway.
关键词
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丹参酮IIA /
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急性肝损伤 /
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PI3K/Akt/Nrf2/HO-1通路 /
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抗氧化
Key words
Tanshinone ⅡA /
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Acute liver injury /
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PI3K/Akt/Nrf2/HO-1 pathway /
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Antioxidation
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基金
国家自然科学基金面上项目(31371090)；湖北省卫生健康科研基金(WJ2021M217)；江汉大学2022年度大学生科研重点项目(2022zd053；2022zd059)
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