基于TLR4/NF-κB途径的白藜芦醇减轻LPS致小鼠急性肺损伤的机制研究
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篇名: 基于TLR4/NF-κB途径的白藜芦醇减轻LPS致小鼠急性肺损伤的机制研究
TITLE: Study on the Mechanism of Resveratrol Attenuating LPS-induced Acute Lung Injury in Mice Based on TLR 4/ NF-κB Pathway
摘要: 目的:观察白藜芦醇(Res)对脂多糖致急性肺损伤(ALI)小鼠的保护作用,并基于Toll样受体(TLR4)/核因子κB(NF-κB)途径探讨其可能机制。方法:将昆明种小鼠分为正常组、模型组、阳性对照组(地塞米松,0.5mg/kg)以及Res低、中、高剂量组(50、100、200mg/kg),每组10只。正常组和模型组小鼠均灌胃生理盐水,每日1次,连续7d;阳性对照组小鼠腹腔注射地塞米松磷酸钠注射液,每日1次,连续3d;Res各剂量组小鼠灌胃相应药物,每日1次,连续7d。末次给药后,除正常组外的其余各组小鼠均于鼻内滴注LPS(5mg/kg)以复制ALI模型。采用Hoechst33242染色法观察各组小鼠肺泡灌洗液中的中性粒细胞凋亡情况,使用流式细胞术检测其凋亡率;采用酶联免疫吸附测定法检测血浆中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量;计算肺湿质量/干质量(W/D)比值;采用苏木精-伊红染色法观察肺组织的形态学特征;采用Westernblotting法检测肺组织中TLR4、NF-κB的表达情况。结果:正常组小鼠肺泡灌洗液中凋亡中性粒细胞较少,肺组织结构完整,未见水肿、充血、渗出、炎症细胞浸润及其他炎症表现。模型组小鼠肺泡灌洗液中凋亡中性粒细胞明显增多,凋亡率显著升高(P<0.01);肺组织水肿、充血明显,并可见红色实变区;血浆IL-6和TNF-α含量、肺W/D比值、肺组织中TLR4和NF-κB的相对表达量均显著升高(P<0.01)。与模型组比较,各给药组小鼠肺泡灌洗液中凋亡中性粒细胞明显增多,凋亡率显著升高(P<0.05或P<0.01);肺组织上述症状均有不同程度的改善;血浆中IL-6和TNF-α含量、肺W/D比值以及肺组织中TLR4、NF-κB的相对表达量(除Res低剂量组外)均显著降低(P<0.05或P<0.01)。结论:Res对ALI模型小鼠具有一定的保护作用,其作用机制可能与抑制TLR4、NF-κB表达、从而减少炎症因子TNF-α、IL-6分泌有关。
ABSTRACT: OBJECTIVE:To observe the p rotective effects of resveratrol (Res)on LPS-induced acute lung injury (ALI)model mice,and to explore its possible mechanism based on TLR 4/NF-κB pathway. METHODS:Kunming mice were divided into normal group,model group ,positive control group (dexamethasone,0.5 mg/kg),Res low-dose ,medium-dose and high-dose groups (50, 100,200 mg/kg),with 10 mice in each group. Normal group and model group were given normal saline intragastrically ,once a day,for 7 days;positive control group were intraperitoneally injected with Dexamethasone sodium phosphate injection ,once a day,for 3 days;Res groups were given relevant medicine intragastrically ,once a day ,for 7 days. After last administration ,all the mice except the normal group were dripped LPS (5 mg/kg)into the nose to induce ALI model. The apoptosis of neutrophils in BALF was observed by Hoechst 33242 staining;the apoptosis rate of neutrophils were detected by flow cytometry. The contents of IL- 6 and TNF-α in the plasma were detected by ELISA. After wet mass to dry mass (W/D)ratio of lung was E-mail:492234709@qq.com calculated,the morphological characteristics of lung tissue were observed by HE staining. Western blotting assay was used to detect the expression o f TLR 4 and NF-κ B in lung tissue. RESULTS :In normal group ,there were few apoptotic neutrophils in the BALF ,and the lung tissue structure was intact , without edema,hyperemia,exudation,inflammatory cell infiltration or other inflammatory manifestations. In model group ,the number of apoptotic neutrophils in BALF increased ,and the apoptotic rate of neutrophils were enhanced significantly (P<0.01); edema and hyperemia of lung tissue were significantly increased ,and the red consolidation area was observed ;the contents of IL- 6 and TNF-α in plasma,the ratio of lung W/D,the relative expression of TLR 4 and NF-κB in lung tissue were significantly increased (P<0.01). Compared with model group ,the number of apoptotic neutrophils in BALF were increased ,and the apoptotic rate of neutrophils were enhanced significantly (P<0.05 or P<0.01)above symptoms of lung tissue were improved to different extents ; the contents of IL- 6 and TNF-α in plasma,lung W/D ratio as well as relative expression of TLR 4 and NF-κB in lung tissue(except for Res low-dose group )in administration groups were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS :Res has a protective effect on ALI model mice ,the mechanism of which may be related to reducing the generation of inflammatory cytokines TNF-α and IL-6 by inhibiting TLR 4/NF-kB expression.
期刊: 2020年第31卷第09期
作者: 杨世勇,何毅,宋大强,吴旭,章卓
AUTHORS: YANG Shiyong ,HE Yi,SONG Daqiang ,WU Xu,ZHANG Zhuo
关键字: 白藜芦醇;急性肺损伤;Toll样受体4;核因子κB;炎症因子;机制;小鼠
KEYWORDS: Resveratrol;Acute lung injury ;TLR4;NF-κB;Inflammatory cytokines ;Mechanism;Mice
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