基于TLR4通路初探黄芩对内毒素血症大鼠肝肺组织中细胞因子IL-1β、IL-6、TNF-a以及氧化应激因子MDA、SOD水平的影响  

Effect of Scutellaria baicalensis Georgi on IL-1β,IL-6,TNF-a,MDA and SOD in liver and lung of endotoxemia rats based on TLR4 signaling pathway

作　　者：陈文[1] 王沛明[1] 张祎[1] 曾勇[1] 叶晓林[1] 

机构地区：[1]成都中医药大学药学院,成都610075

出　　处：《中药药理与临床》2016年第3期87-92,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81274111);四川省科技厅省青年科技创新研究团队专项计划项(2014TD0007)

摘　　要：目的:研究黄芩对内毒素血症模型大鼠肝肺脏器氧化应激及炎性损伤的保护作用。方法:将56只SD大鼠随机分为空白对照组、模型对照组、地塞米松阳性对照组(7.5×10-4g/kg)、黄芩组(10 g/kg)、黄芩组(5 g/kg)、黄芩组(1.5 g/kg)、黄芩组(0.75 g/kg)。每天早晚各给药一次,连续给药7次,于末次给药0.5h后尾静脉注射脂多糖(LPS)(5 mg/kg)生理盐水溶液建立内毒素血症模型,然后每0.5 h测量一次肛温,记录体温变化趋势,于造模后6 h处死动物,测定脾脏和胸腺的脏器系数,肝、肺组织湿重/干重比(W/D)及其含水百分比,以及肝肺组织中丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活力;采用酶联免疫吸附法(ELISA)检测肝肺组织中细胞因子白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的含量;运用Western Blot和qRTPCR检测肝肺脏中TLR4蛋白和mRNA的相对表达情况。结果:模型大鼠肝肺脏中TLR4蛋白的表达、IL-1β、IL-6、TNF-α、MDA含量均明显升高,而SOD的活力显著下降,表明模型动物体内存在一定程度的氧化应激及炎症反应。黄芩1.5 g/kg能显著升高肝脏和肺脏中SOD活力,同时降低肝肺脏中MDA、IL-1β、TNF-α的含量及下调TLR4蛋白和基因的表达。结论:黄芩可能通过下调肝肺组织炎症信号通路中TLR4蛋白的表达来阻止炎症信号的转导,从而减少下游细胞因子IL-1β、TNF-α的表达以及过度累积的自由基而发挥对内毒素血症大鼠肝肺损伤的保护作用。Objective： To explore the protective effect of Scutellaria baicalensis Georgi on oxidativestress and inflammatory injury in LPS-induced a- cute endotoxemia rats in lung and liver. Methods ：56 SD rats were randomly divided into contral group, model group, Dexamethasone group（ 7. 5×10 ug/kg ） , Scutellaria baicalensis Georgi group （ 10 g/kg）, ScuteUaria baicalensis Georgi group （ 5 g/kg）, Scutellaria baicalensis Georgi group（ 1.5 g/kg） ,Scutellaria haicalensis Georgi group（0.75 g/kg）. All of animals were administered continuously for 7 times twice a day, once in morning and the other in evening. Acute endotoxemia models were established by tail intravenous injection of LPS （5mg/kg body weight ） after the last administration 0.5 h, then rats were tested rectal temperature once every 0.5 h. At 6h after injecting LPS, animals wre ex- ecuted and then weighed to calculate the organ coefficient of spleen and thymus, determined the wet/dry weight ratio （W/D） , water percenta- ges ,the content of malondialdehyde （MDA） and the activity of superoxide dismutase （SOD） of liver and lung. The contents of proiaflamma- tory cytokines（ IL-1β, IL-6, TNF-α）in liver and lung were determined by ELISA. Theexpression of TLR4 was determined by Western Blot and qRT-PCR. Results： The content of IL-1β ,IL-6 ,TNF-α, MDA and TLR4 protein expression in liver and lung of endotoxemia rats were significantly increased （ P 〈 0.05 or P 〈 0.01 ）, and the activity of SOD was markly declined （ P 〈 0.05 or P 〈 0.01 ）, those showed that there was a certain degree of oxidative stress and inflammatory injury in endotoxemia model rats. Scutellaria baicalensis Georgi（1.5g/kg） can sig- nificantly enhance the activity of SOD in liver and lung （ P 〈 0.05 ）, and reduce the content of MDA, IL-Iβ, TNF-α and TLR4 protein expres- sion in lung and liver of endotoxemia rats （ P 〈 0.05）. Conclusions： Scutellaria baicalensis Georgi can protect lung and liver from LPS-in- duced acute e

关 键 词：黄芩 内毒素血症 TLR4 氧化应激 细胞因子 

分 类 号：R285.5[医药卫生—中药学]