文献类型：期刊文献

中文题名：基于TLR2/4-NF-κB/iNOS-NO信号通路研究秦艽水提物对胶原诱导型关节炎大鼠的影响及作用机制

英文题名：Effects and Mechanism of Aqueous Extract from Gentiana macrophylla Pall.on Collagen Induced Arthritis Rats Based on TLR2/4-NF-κB/iNOS-NO Signaling Pathway

作者：马晓辉[1];张可锋[1];朱田田[1];曹后康[1];何微微[1];晋玲[1]

第一作者：马晓辉

机构：[1]甘肃中医药大学,兰州730000

第一机构：甘肃中医药大学

年份：2020

卷号：36

期号：5

起止页码：110

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家自然科学基金(编号:81860673);甘肃省基础研究创新群体项目(编号:1606RJIA323);广西高校科学技术研究项目(编号:KY2015YB215);科技基础性工作专项子课题(编号:2013FY114500)。

语种：中文

中文关键词：秦艽水提物;胶原诱导型关节炎(CIA);Toll样受体2/4-核转录因子/诱导型一氧化氮合酶-一氧化氮(TLR2/4-NF-κB/iNOS-NO)信号通路;抗炎

外文关键词：Aqueous Extract of Gentiana macrophylla Pall;collagen induced arthritis(CIA);TLR2/4-NF-κB/iNOS-NO signaling pathway;anti-inflammatory

摘要：目的:研究秦艽水提物对胶原诱导型关节炎(CIA)大鼠的疗效,并从Toll样受体2/4-核转录因子/诱导型一氧化氮合酶一氧化氮(TLR2/4-NF-κB/iNOS-NO)信号通路探讨其可能的作用机制。方法:SD大鼠随机分为6组,即正常对照组、模型对照组、雷公藤多苷0.005 g/kg组、秦艽水提物8 g/kg、4 g/kg、2 g/kg组。除正常对照组外,其余大鼠均建立CIA大鼠模型。模型成功后,药物组按对应剂量灌胃给药,正常对照组及模型对照组以等体积(10 ml/kg)灌胃双蒸水,每天1次,共28 d。观察并记录实验期间大鼠体重变化及右踝关节肿胀程度;Elisa法检测大鼠血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)及一氧化氮(NO)含量;Western blot测定大鼠足跖软组织中核转录因子-κB(NF-κB)、Toll样受体2(TLR2)和Toll样受体4(TLR4)相关蛋白表达变化。结果:与正常对照组相比,模型对照组血清中IL-1β、IL-6、TNF-α、iNOS及NO含量显著升高;足跖软组织中NF-κB、TLR2及TLR4相关蛋白表达明显上调(P<0.05或P<0.01)。药物干预28 d后,与模型对照组相比,除秦艽水提物2 g/kg组外,其余各给药组大鼠体重显著升高,踝关节肿胀程度显著降低;血清中IL-1β、IL-6、TNF-α、iNOS及NO含量显著下降;足跖软组织中NF-κB、TLR2及TLR4相关蛋白的表达明显下调(P<0.05或P<0.01)。结论:秦艽水提物对大鼠胶原诱导型关节炎有显著的治疗作用,其作用机制可能与抑制TLR2/4-NF-κB/iNOS-NO信号通路,进而抑制炎症反应有关。
Objective:To study the therapeutic effect of aqueous extract from Gentiana macrophylla Pall.on collagen induced arthritis(CIA)rats and to explore its mechanism based on TLR2/4-NF-κB/iNOS-NO signaling pathway.Methods:SD rats were randomly divided into 6 groups:the control group,the model group,Tripterygium glycoside(5 mg/kg)group and aqueous extract from different doses of Gentiana macrophylla Pall.groups(8 g/kg,4 g/kg,2 g/kg).Except for the control group,all other rats were used to establish collagen-induced arthritis(CIA)rat model.After modeling,rats were given corresponding drugs or double distilled water at the same volume by gavage,once a day for 28 days.The changes of body weight and the degree of right ankle joint swelling were observed and recorded during this experiment.ELISA technique was used to detect the contents of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),inducible nitric oxide synthetase(iNOS)and nitric oxide(NO).Nuclear factor-κB(NF-κB),Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)protein expression levels in the foot soft tissue of rats were detected by Western blot.Results:Compared with the control group,the levels of IL-1β,IL-6,TNF-α,iNOS and NO in the serum of rats in the model group were significantly increased,the expressions of NF-κB,TLR2 and TLR4 related proteins in the soft tissues of the feet were significantly increased(P<0.05 or P<0.01).After 28 days of drug intervention,compared with the model group,except for 2 g/kg Gentiana macrophylla Pall.group,the rat weight in each group was significantly increased,the swelling degree of ankle joint was significantly decreased.The contents of IL-1β,IL-6,TNF-α,iNOS and NO in serum were significantly decreased.The expressions of NF-κB,TLR2 and TLR4 related protein in the soft tissues of feet were significantly decreased(P<0.05 or P<0.01).Conclusion:The aqueous extract from Gentiana macrophylla Pall.has a significant therapeutic effect on collagen-induced arthritis in rats,and its mechanism may be related to the inhibition of TLR2/4-NF-κB/iNOS-NO signal pathway and the inhibition of inflammatory response.