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瑞舒伐他汀通过靶向铁死亡、热休克蛋白B1和炎症来改善化学诱导的大鼠急性肺损伤。

Rosuvastatin ameliorates chemically induced acute lung injury in rats by targeting ferroptosis, heat shock protein B1, and inflammation.

作者信息

Abdallah Hana H, Abd El-Fattah Eslam E, Salah Neven A, El-Khawaga Omali Y

机构信息

Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.

Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1883-1894. doi: 10.1007/s00210-024-03352-9. Epub 2024 Aug 27.

Abstract

Acute lung injury (ALI) is a life-threatening condition characterized by respiratory failure. Rosuvastatin (RSV) is an antihypercholesterolemic agent with antioxidant properties. The current study aimed to investigate RSV novel therapeutic impact on ALI with emphasis on oxidative stress, inflammation, and heat shock protein B1 (HSPB1). Male albino rats (N = 30) were divided into five groups. Normal control (NC) group: rats received normal saline 2 mL/kg P.O daily. Lipopolysaccharides (LPS) group: rats received LPS (3 mg/kg intraperitoneally once). RSV group: rats received RSV (2 mg/kg P.O daily). LPS + RSV group: rats received RSV as in group 3 and on the 7th day rats received LPS as group 2. LPS + Dexamethasone (DX): rats received DX (2 mg/kg P.O, daily for one week) and on the 7th day rats received LPS as group 2. At the end of experiment (one week), lung tissue was used to determine HSPB1, high mobility group box 1 (HMGB1) using ELISA. IL-6, nuclear factor-2 (Nrf2), haem Oxygenase-1 (HO-1) protein levels were assessed using immunohistochemistry. GSH, catalase, MDA, NO, albumin and urea are assessed by colorimetry. The results revealed that RSV treatment resolved histopathological changes in lung tissue induced by LPS. Compared to LPS group, LPS + RSV group showed significant decrease in urea, NO, MDA, HMGB1, IL-6 and HO-1 level compared to LPS-treated rats. Conversely, RSV treatment significantly increased HSPB1, Nrf2, albumin, GSH, and CAT levels compared to LPS rats. RSV is effective for amelioration of ALI and thus can be used as adjuvant therapy for ALI.

摘要

急性肺损伤(ALI)是一种以呼吸衰竭为特征的危及生命的病症。瑞舒伐他汀(RSV)是一种具有抗氧化特性的抗高胆固醇血症药物。本研究旨在探讨RSV对ALI的新型治疗作用,重点关注氧化应激、炎症和热休克蛋白B1(HSPB1)。将雄性白化大鼠(N = 30)分为五组。正常对照组(NC):大鼠每日经口给予2 mL/kg生理盐水。脂多糖(LPS)组:大鼠腹腔注射一次LPS(3 mg/kg)。RSV组:大鼠每日经口给予RSV(2 mg/kg)。LPS + RSV组:大鼠按第3组给予RSV,在第7天按第2组给予LPS。LPS + 地塞米松(DX)组:大鼠每日经口给予DX(2 mg/kg,持续一周),在第7天按第2组给予LPS。在实验结束时(一周),使用肺组织通过酶联免疫吸附测定法测定HSPB1、高迁移率族蛋白B1(HMGB1)。使用免疫组织化学评估白细胞介素-6、核因子E2相关因子(Nrf2)、血红素加氧酶-1(HO-1)蛋白水平。通过比色法评估谷胱甘肽(GSH)、过氧化氢酶、丙二醛(MDA)、一氧化氮(NO)、白蛋白和尿素。结果显示,RSV治疗缓解了LPS诱导的肺组织组织病理学变化。与LPS组相比,LPS + RSV组与LPS处理的大鼠相比,尿素、NO、MDA、HMGB1、白细胞介素-6和HO-1水平显著降低。相反,与LPS大鼠相比,RSV治疗显著提高了HSPB1、Nrf2、白蛋白、GSH和过氧化氢酶水平。RSV对改善ALI有效,因此可作为ALI的辅助治疗药物。

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