沙奎那韦对机械通气引起小鼠肺损伤的保护作用与高迁移率族蛋白B1有关
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High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice
背景与目的
沙奎那韦（SQV）是FDA批准的第一种HIV蛋白酶抑制剂。之前研究表明SQV可以限制Toll样受体-4（TLR4）介导的炎症通路和核因子-κB（NF-κB）的激活，从而在多种疾病中起到保护作用。高迁移率族蛋白B1（HMGB1）是一种炎症介质，并可能在呼吸机引起的肺损伤（VILI）后短时间内表达其毒性。
方 法
本研究将C57BL / 6小鼠随机分为4组（n = 10）：对照组和SQV组（Con + SQV），均为自主呼吸。HTV组（HTV）接受高潮气量通气（HTV）4小时，HTV联合SQV组（HTV + SQV）在HTV前7天用5mg / kg的SQV预处理。HTV 4小时后处死小鼠。测定肺湿/干重（W / D）比、肺泡 - 毛细血管对伊文思蓝白蛋白的通透性（EBA）、细胞计数、支气管肺泡灌洗液（BALF）中的总蛋白、肿瘤坏死因子-α（TNF-α）、BALF和肺组织中白细胞介素-6（IL-6）的水平以及观察肺组织病理学变化。
结 果
结果表明HTV可激活NF-κB并引起显著的肺损伤，这与BALF和血浆中TNF-α和IL-6水平的升高有关。SQV预处理可显著减少肺部炎性损伤以及抑制NF-κB激活。
结 论
该结果表明SQV的保护作用可能与抑制小鼠中NF-κB的激活和HMGB1的表达有关。
原始文献摘要
Wang, Renlingzi, Zhang, et al. High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice[J]. 生物化学与生物物理学报(英文), 2017, 49(10):907-915.
Abstract.
1.Saquinavir (SQV) is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 (TLR4)-mediated inflammatory pathway and nuclear factor-κB (NF-κB)
activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1(HMGB1) has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury (VILI).
2. In this study, C57BL/6 mice were randomly divided into four groups (n = 10): control group and control with SQV group (Con + SQV) were spontaneous breath. HTV group (HTV) received high tidal volume ventilation (HTV) for 4 h. HTV with SQV group (HTV + SQV) were pretreated with 5mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight (W/D) ratio, alveolar-capillary permeability to Evans blue albumin (EBA), cell counts, total proteins in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) level in BALF and lung tissue, and lung histopathology were examined.
3. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation.
4. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.
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