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雪松醇可改善脂多糖诱导的大鼠全身炎症和肺损伤。

Cedrol ameliorates lipopolysaccharide-induced systemic inflammation and lung injury in rats.

作者信息

Behrouz Sepide, Hosseini Mahmoud, Rezaee Ramin, Boskabady Mohammad Hossein, Asgharzadeh Fereshteh, Gholamnezhad Zahra

机构信息

Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Eur J Pharmacol. 2025 Sep 15;1003:177952. doi: 10.1016/j.ejphar.2025.177952. Epub 2025 Jul 15.

DOI:10.1016/j.ejphar.2025.177952
PMID:40675359
Abstract

Cedrol is sesquiterpene alcohol with anti-inflammatory and antioxidant properties; this study evaluated cedrol protective effects against lipopolysaccharide (LPS)-induced systemic inflammation and lung damage. Forty male rats were randomized into the following groups: control (saline); LPS (1 mg/kg); and LPS + cedrol 7.5, 15, and 30 mg/kg. Cedrol was administered for 2 weeks (day 1-14, once daily, orally) while LPS was injected on days 8-14 (once daily, intraperitoneally). Finally, blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. White blood cells (WBC) counts, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, oxidative stress markers, and nitric oxide (NO) levels were determined, and lung histopathological changes were evaluated. LPS significantly increased total WBC, neutrophil and monocyte counts, and the levels of TNF-α, IL-1β and malondialdehyde (MDA), while significantly reduced total thiol content, and catalase (CAT) and superoxide dismutase (SOD) activity in serum compared to the control group. The highest dose of cedrol significantly reduced total WBC, neutrophil, lymphocyte, and monocyte counts, downregulated the levels of TNF-α, IL-1β and MDA, but increased total thiol content, and CAT and SOD activity, compared to the LPS group. In the lung, LPS induced histopathological injury, and it significantly increased BALF total and differential WBC counts and TNF-α, NO, and MDA levels, while reducing thiol content, and CAT and SOD activity, compared to the control group; cedrol dose-dependently reversed all these changes. It is concluded that cedrol dose-dependently ameliorated LPS-induced systemic and lung inflammation and oxidative stress.

摘要

雪松醇是一种具有抗炎和抗氧化特性的倍半萜醇;本研究评估了雪松醇对脂多糖(LPS)诱导的全身炎症和肺损伤的保护作用。40只雄性大鼠被随机分为以下几组:对照组(生理盐水);LPS组(1mg/kg);以及LPS + 雪松醇7.5、15和30mg/kg组。雪松醇给药2周(第1 - 14天,每日一次,口服),而LPS在第8 - 14天注射(每日一次,腹腔注射)。最后,获取血液、支气管肺泡灌洗液(BALF)和肺组织样本。测定白细胞(WBC)计数、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、氧化应激标志物和一氧化氮(NO)水平,并评估肺组织病理学变化。与对照组相比,LPS显著增加了总WBC、中性粒细胞和单核细胞计数,以及TNF-α、IL-1β和丙二醛(MDA)水平,同时显著降低了血清中的总硫醇含量、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性。与LPS组相比,最高剂量的雪松醇显著降低了总WBC、中性粒细胞、淋巴细胞和单核细胞计数,下调了TNF-α、IL-1β和MDA水平,但增加了总硫醇含量、CAT和SOD活性。在肺中,LPS诱导了组织病理学损伤,与对照组相比,它显著增加了BALF中总WBC和分类WBC计数以及TNF-α、NO和MDA水平,同时降低了硫醇含量、CAT和SOD活性;雪松醇剂量依赖性地逆转了所有这些变化。结论是,雪松醇剂量依赖性地改善了LPS诱导的全身和肺部炎症以及氧化应激。

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