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缺血后处理用反式白藜芦醇对大鼠肝细胞因子产生和中性粒细胞募集的保护作用。

Protective effect of post-ischemic treatment with trans-resveratrol on cytokine production and neutrophil recruitment by rat liver.

机构信息

Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'Observatoire, Paris, France.

出版信息

Biochimie. 2010 Apr;92(4):405-10. doi: 10.1016/j.biochi.2009.12.009. Epub 2009 Dec 24.

Abstract

Oxidative and inflammatory processes are elicited during hepatic post-ischemic reperfusion and generate liver damage. This study investigated the early anti-inflammatory effect of trans-resveratrol (T-res) and its consequences on the late self-aggravating inflammatory process in liver ischemia-reperfusion (I/R). Partial hepatic ischemia was initiated in rats for 1 h and T-res (0.02 and 0.2 mg/kg) was administered intravenously 5 min before starting reperfusion for 3 h. Plasma levels of aminotransferases and cytokines (tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6) and hepatic neutrophil recruitment were assessed. Hepatic expression of stress protein (heat-shock protein (HSP-70), heme oxygenase-1(HO-1)) and cytokine (TNF-alpha, IL-1beta, keratinocyte chemoattractant (KC)) mRNA was investigated. I/R caused an increase in aminotransferase levels and increased polymorphonuclear cell infiltration. Post-ischemic treatment with T-res (0.02 and 0.2 mg/kg) resulted in a significant decrease in aminotransferase, IL-1beta and IL-6 plasma levels by about 40%, 60% and 40%, respectively, compared to the vehicle I/R group. Post-ischemic treatment with T-res (0.02 mg/kg) also significantly decreased hepatic neutrophil recruitment. TNF-alpha, IL-1beta, KC and HO-1 hepatic mRNA expression was reduced by T-res without any change in HSP-70 mRNA. This T-res mediated decrease in early release of cytokines and neutrophil recruitment led to a reduction in the late inflammatory process. T-resveratrol might be useful in the prevention of inflammation secondary to hepatic surgery or liver transplantation.

摘要

氧化和炎症过程在肝缺血再灌注后被引发,并产生肝损伤。本研究调查了反式白藜芦醇(T-res)的早期抗炎作用及其对肝缺血再灌注(I / R)后期自我加重炎症过程的影响。大鼠进行部分肝缺血 1 小时,然后在再灌注前 5 分钟静脉内给予 T-res(0.02 和 0.2 mg/kg),持续 3 小时。评估血浆转氨酶和细胞因子(肿瘤坏死因子(TNF)-α,白细胞介素(IL)-1β,IL-6)水平和肝中性粒细胞募集。研究了应激蛋白(热休克蛋白(HSP)-70,血红素加氧酶-1(HO-1))和细胞因子(TNF-α,IL-1β,角质细胞化学引诱剂(KC))mRNA 的肝表达。I / R导致转氨酶水平升高和多形核细胞浸润增加。与 vehicle I / R 组相比,T-res(0.02 和 0.2 mg/kg)在缺血后处理可使转氨酶,IL-1β和 IL-6 的血浆水平分别降低约 40%,60%和 40%。缺血后用 T-res(0.02 mg/kg)处理还可显著减少肝中性粒细胞募集。TNF-α,IL-1β,KC 和 HO-1 的肝 mRNA 表达被 T-res 降低,而 HSP-70 mRNA 无变化。T-res 介导的早期细胞因子和中性粒细胞募集减少导致晚期炎症过程减少。T-resveratrol 可能对预防肝外科手术或肝移植后的炎症有用。

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