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姜黄素通过抑制 NF-κB、iNOS 和 ICAM-1 的表达来减轻干热环境中热射病引起的大鼠肝损伤。

Curcumin alleviates heatstroke-induced liver injury in dry-heat environments by inhibiting the expression of NF-κB, iNOS, and ICAM-1 in rats.

机构信息

Key Laboratory of Special Environmental Medicine of Xinjiang, Urumqi, China.

Graduate School of Xinjiang Medical University, Urumqi, China.

出版信息

PLoS One. 2024 Sep 6;19(9):e0309598. doi: 10.1371/journal.pone.0309598. eCollection 2024.

Abstract

we aimed to monitor liver injury in rat model during heat stress and heatstroke in dry-heat environment and investigate the effects of curcumin on heatstroke-induced liver injury and the underlying mechanisms. Sprague-Dawley (SD) rats were randomly divided into four groups: normal saline (NS), and 50 (50-cur), 100 (100-cur), and 200 mg/kg curcumin (200-cur) groups. They were administered the indicated doses of curcumin by gavage once daily for 7 days. On day 8, the rats were transferred to a simulated climate cabin, At 0, 50, 100, and 150 min, the core temperature (Tc) was measured respectively. After sacrificing the rats, tissue samples were collected, measure histology indices, serum enzymes, lipopolysaccharides (LPSs), cytokines, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). The Tc increased with time in all groups. Curcumin alleviation of symptoms and improvement in pathological scores. The level of enzymes, LPS, and cytokines increased during heatstroke in the NS group, but curcumin decreased the levels of these indicators. The differences of the indicators between NS and 200-cur groups at 150 min were significant (P < 0.05). The expression of NF-κB p65, iNOS, and ICAM-1 was upregulated in the NS group at 150 min, but their expression was relatively lower in the curcumin groups (P < 0.05). Thus, our findings indicate acute liver injury during heat stress and heatstroke. The mechanism involves cascade-amplification inflammatory response induced by the gut endotoxin. Furthermore, curcumin alleviated heatstroke-induced liver injury in a dose-dependent manner by downregulating NF-κB, iNOS, and ICAM-1.

摘要

目的

在干热环境中监测热应激和中暑大鼠模型中的肝损伤,并研究姜黄素对中暑诱导的肝损伤的影响及其机制。

方法

SD 大鼠随机分为四组:生理盐水(NS)组和 50(50-cur)、100(100-cur)和 200mg/kg 姜黄素(200-cur)组。它们通过灌胃每天给予指定剂量的姜黄素一次,共 7 天。第 8 天,大鼠被转移到模拟气候舱中,分别在 0、50、100 和 150 分钟时测量核心温度(Tc)。处死大鼠后,收集组织样本,测量组织学指标、血清酶、脂多糖(LPS)、细胞因子、核因子-κB(NF-κB)、诱导型一氧化氮合酶(iNOS)和细胞间黏附分子-1(ICAM-1)。

结果

所有组的 Tc 均随时间增加。姜黄素缓解症状和改善病理评分。在 NS 组,中暑时酶、LPS 和细胞因子水平升高,但姜黄素降低了这些指标的水平。在 150 分钟时,NS 组和 200-cur 组之间的指标差异具有统计学意义(P<0.05)。在 150 分钟时,NS 组 NF-κB p65、iNOS 和 ICAM-1 的表达上调,但姜黄素组的表达相对较低(P<0.05)。

结论

我们的研究结果表明在热应激和中暑过程中存在急性肝损伤。其机制涉及由肠道内毒素诱导的级联放大炎症反应。此外,姜黄素通过下调 NF-κB、iNOS 和 ICAM-1 以剂量依赖的方式缓解中暑诱导的肝损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b7/11379272/8a95f3e5b144/pone.0309598.g001.jpg

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