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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 |
| 阅读数： | 341 次 |
| 本月下载数： | 6 次 |
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