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豆甾醇抑制脂多糖诱导的小鼠模型固有免疫反应。

Stigmasterol inhibits lipopolysaccharide-induced innate immune responses in murine models.

机构信息

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science & Technology, KNUST, Kumasi, Ghana.

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science & Technology, KNUST, Kumasi, Ghana.

出版信息

Int Immunopharmacol. 2017 Dec;53:105-113. doi: 10.1016/j.intimp.2017.10.018.

DOI:10.1016/j.intimp.2017.10.018
PMID:29078089
Abstract

Stigmasterol is a naturally occurring steroid alcohol which occurs in vegetables, soya and a large variety of medicinal plants. Stigmasterol and other phytosterols have been documented as immunomodulators with huge therapeutic potential. We assessed the mitigating effect of stigmasterol on non-fatal and fatal innate immune responses in murine models after intraperitoneal challenge with an endotoxin, lipopolysaccharide, LPS. The effect of stigmasterol on LPS-induced febrile response, inflammatory cell proliferation, multiple organ damage and mortality were respectively investigated. Pretreatment with stigmasterol 10, 50 and 100mg/kg reduced total LPS-induced fever response by 39.93±10.52%, 53.05±5.84% and 77.27±6.25% respectively. Neutrophil proliferation both in blood and recovered peritoneal fluid was significantly reversed by stigmasterol at 50 and 100mg/kg. Lung and liver histopathology showed stigmasterol effectively controlled organ damage. The lung inflammation score of 9.20±0.73 for the polyethylene glycol, PEG-treated disease control mice was reduced respectively to 6.50±0.54, 4.60±0.40 and 4.10±0.42 with 10, 50 and 100mg/kg of stigmasterol. Serum levels of liver enzyme markers, alanine transaminase, ALT and aspartate transaminase, AST were consistent with the observed histological changes. Stigmasterol at 50 and 100mg/kg significantly protected mice from LPS-induced mortality with 40% survival. Overall, stigmasterol inhibits LPS-induced innate immune responses in murine models.

摘要

豆甾醇是一种天然存在的甾体醇,存在于蔬菜、大豆和多种药用植物中。豆甾醇和其他植物甾醇已被证明具有免疫调节作用,具有巨大的治疗潜力。我们评估了豆甾醇对内毒素、脂多糖(LPS)腹腔内攻击后小鼠模型中非致命性和致命性固有免疫反应的缓解作用。分别研究了豆甾醇对 LPS 诱导的发热反应、炎症细胞增殖、多器官损伤和死亡率的影响。10、50 和 100mg/kg 的豆甾醇预处理分别使总 LPS 诱导的发热反应降低了 39.93±10.52%、53.05±5.84%和 77.27±6.25%。在血液和回收的腹腔液中,豆甾醇均能显著逆转中性粒细胞增殖。肺和肝组织病理学显示,豆甾醇能有效控制器官损伤。聚乙二醇(PEG)处理的疾病对照组小鼠的肺炎症评分从 9.20±0.73 分别降低至 6.50±0.54、4.60±0.40 和 4.10±0.42,使用 10、50 和 100mg/kg 的豆甾醇。肝酶标志物丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的血清水平与观察到的组织学变化一致。50 和 100mg/kg 的豆甾醇可显著保护小鼠免受 LPS 诱导的死亡,存活率为 40%。总体而言,豆甾醇抑制了小鼠模型中 LPS 诱导的固有免疫反应。

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