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人工合成红景天苷对大鼠急性肺损伤的保护作用

黄倩, 蔡艳春, 危晓莉, 吴金龙, 梅汝焕, 胡晓兰

浙江大学医学院生理学系，杭州 310058；化学系，杭州 310027

摘要

为了研究人工合成红景天苷(salidroside, Sal)对脂多糖(lipopolysaccharide, LPS)诱导大鼠急性肺损伤(acute lung injury, ALI)的保护作用及其机制，将雄性Sprague-Dawley大鼠随机分为生理盐水对照组、3 mg/kg LPS损伤组、不同剂量Sal干预组(5、20和80 mg/kg)以及5 mg/kg地塞米松(dexamethasone, Dex)干预组，气管内滴注LPS建立ALI 模型，在LPS造模前0.5 h腹腔给予人工合成Sal或Dex，造模6 h后处死动物。计量肺湿/干重比值(wet/dry weight ratio, W/D)，苏木素-伊红染色观测肺组织病理形态学变化和肺损伤评分。用瑞氏染色计数肺泡灌洗液(bronchoalveolar lavage fluid, BALF)离心沉淀的中性粒细胞(polymorphonuclear leukocyte, PMN)，用BCA法测定BALF离心上清蛋白含量，并用酶联免疫吸附法测定TNF-α、IL-1β和IL-6的含量。测定肺组织中髓过氧化物酶(myeloperoxidase, MPO)和丙二醛(malondialdehyde, MDA)含量，Western blot检测肺组织中磷酸化NF-κB和总NF-κB蛋白表达水平。结果显示，与LPS组比较，人工合成Sal能减轻肺组织损伤程度，降低肺损伤评分和W/D比值(P < 0.05)，减少BALF中PMN计数、蛋白含量以及炎症因子水平(P < 0.05)，降低肺组织中MPO和MDA含量(P < 0.05)，抑制肺组织中磷酸化NF-κB蛋白的表达(P < 0.05)。以上结果提示，人工合成Sal对LPS诱导的ALI具有保护作用，其机制与抑制肺组织NF-κB蛋白磷酸化以及减少PMN在肺内聚集有关。

关键词： 红景天苷; 脂多糖 ; 急性肺损伤 ; 大鼠

分类号：Q291

Protective effect of synthetic salidroside on acute lung injury in rats

HUANG Qian, CAI Yan-Chun, WEI Xiao-Li1, WU Jin-Long, MEI Ru-Huan, HU Xiao-Lan

Department of Physiology, School of Medicine, Zhejiang University, Hangzhou 310058, China；2Department of Chemistry, Zhejiang University, Hangzhou 310027, China

Abstract

To study the protective effect and mechanism of synthetic salidroside on acute lung injury (ALI) induced by lipopolysaccharide (LPS), male Sprague-Dawley (SD) rats were randomly divided into saline control group, 3 mg/kg LPS model group, different doses of salidroside groups (5, 20 and 80 mg/kg), and 5 mg/kg dexamethasone group. Intratracheal LPS instillation was used to establish the ALI model 0.5 h after intraperitoneal injection of salidroside or dexamethasone, and the rats were sacrificed 6 h later. Lung wet/dry weight ratio (W/D) was calculated. Lung tissue pathology and lung injury score (LIS) were observed and evaluated through hematoxylin and eosin (HE) staining. The centrifugal sediment of bronchoalveolar lavage fluid (BALF) was used to count the polymorphonuclear leukocyte (PMN) number by Wright’s staining, and the centrifugal supernatant of BALF was used to determine the contents of protein and inflammatory factors (TNF-α, IL-1β and IL-6). The contents of myeloperoxidase (MPO) and malondialdehyde (MDA) in lung tissue were determined. Western blot was used to detect the expression levels of phosphorylated and total nuclear factor kappa B (NF-κB)/p65 protein in lung tissue. The results showed that, compared with LPS group, the intervention of synthetic salidroside alleviated the pathological damage in lung tissue, decreased the LIS and lung W/D ratio (P < 0.05), reduced the PMN number, the contents of protein and inflammatory factors in BALF (P < 0.05), reduced the contents of MPO and MDA in lung tissue (P < 0.05), and inhibited the expression of p-NF-κB in lung tissue (P < 0.05). The results suggest that synthetic salidroside has a protective effect on ALI induced by LPS, and its mechanism is related to inhibiting the phosphorylation of NF-κB and reducing the aggregation of PMN in the lung.

Key words: salidroside; lipopolysaccharide ; acute lung injury ; rat

收稿日期：2016-11-04　　录用日期：2017-03-17

通讯作者：胡晓兰　　E-mail: huxiaolan@zju.edu.cn

引用本文：

黄倩, 蔡艳春, 危晓莉, 吴金龙, 梅汝焕, 胡晓兰. 人工合成红景天苷对大鼠急性肺损伤的保护作用[J]. 生理学报 2017; 69 (3): 291-297.

HUANG Qian, CAI Yan-Chun, WEI Xiao-Li1, WU Jin-Long, MEI Ru-Huan, HU Xiao-Lan. Protective effect of synthetic salidroside on acute lung injury in rats. Acta Physiol Sin 2017; 69 (3): 291-297 (in Chinese with English abstract).