红景天苷对LPS诱导的脑内炎症反应的抑制作用机制研究  

Inhibitory mechanism of salidroside on LPS-induced inflammation in brain

作　　者：周彬彬 郑雪蕊 谢志扬 余正双 吴青青 吴慧玲 赖文芳[1] 洪桂祝 ZHOU Bin-bin;ZHENG Xue-rui;XIE Zhi-yang;YU Zheng-shuang;WU Qing-qing;WU Hui-ling;LAI Wen-fang;HONG Gui-zhu(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《中国药理学通报》2023年第11期2096-2101,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82174001,81973503);福建省自然科学基金项目(No 2021J02014,2020J01727);福建省卫健委中青年骨干人才培养项目(No 2019-ZQN-74);2018年福建省教育厅杰青项目。

摘　　要：目的研究红景天苷(salidroside,sal)对脂多糖(lipopolysaccharide,LPS)诱导的炎症反应的作用,并探讨其作用机制。方法(1)健康成年雄性SPF级SD大鼠40只,随机分为假手术组(sham组),红景天苷组(sal组),模型组(LPS组),模型+红景天苷组(LPS+sal组),侧脑室注射LPS 2μL(1 g·L^(-1))制备炎症模型,sal给药浓度为50 mg·kg^(-1)·d^(-1),给药1 d。(2)60只大鼠随机分为假手术组(sham组),假手术+抑制剂组(Sham+LY294002组),模型组(LPS组),模型+抑制剂组(LPS+LY294002组),模型+红景天苷组(LPS+sal组),模型+红景天苷+抑制剂组(LPS+sal+LY294002组)。侧脑室注射抑制剂LY294002,30min后,侧脑室注射2μL LPS(1 g·L^(-1))制备炎症模型。sal给药浓度为50 mg·kg^(-1)·d^(-1),给药1 d。观察中性粒细胞染色情况,蛋白印迹法检测p-Akt、Akt蛋白及核蛋白NF-κB表达,RT-PCR检测TNF-α、IL-1β、CD14、iNOS mRNA的表达。结果与LPS组比较,sal作用后能够降低中性粒细胞浸润水平,促进Akt蛋白磷酸化水平,抑制核蛋白NF-κB的表达,抑制TNF-α、IL-1β、CD14、iNOS mRNA的表达;经PI3K抑制剂LY294002干预后,sal对上述指标作用不明显,表明LY294002作用后能够逆转sal对LPS诱导大鼠脑内炎症模型的抑制作用。结论sal能够减少LPS诱导的中性粒细胞浸润,并通过PI3K/Akt通路,抑制NF-κB核蛋白及炎症因子的表达,从而发挥抗炎作用。Aim To study the effect of salidroside(sal)on lipopolysaccharide(LPS)-induced inflammation and its mechanism.Methods(1)Forty healthy adult male SPF grade SD rats were randomly divided into sham operation group(sham group),salidroside group(sal group),model group(LPS group),model+salidroside group(LPS+sal group).The inflammatory model was prepared by injecting 2μL(1 g·L^(-1))of LPS into the lateral ventricle.The concentration of salidroside was 50 mg·kg^(-1)·d^(-1),and the samples were taken one day after administration.(2)Sixty rats were randomly divided into sham operation group(sham group),sham operation+inhibitor group(sham+LY294002 group),model group(LPS group),model+inhibitor group(LPS+LY294002 group),model+salidroside group(LPS+sal group),model+salidroside+inhibitor group(LPS+sal+LY294002 group).The inhibitor LY294002 was injected into the lateral ventricle,and then LPS(1 g·L^(-1))2μL was injected into the lateral ventricle to prepare the inflammatory model 30 minutes later.Salidroside was administered at a concentration of 50 mg·kg^(-1)·d-1.Samples were taken one day after administration.The staining of neutrophils was observed,and the expressions of p-Akt,Akt protein and NF-κB were detected by Western blot.TNF-α,IL-1β,CD14,iNOS mRNA expressions were detected by RT-PCR.Results Compared with LPS group,salidroside could reduce neutrophil infiltration,promote Akt protein phosphorylation and inhibit nuclear protein NF-κB expression,inhibit TNF-α,IL-1β,CD14,iNOS mRNA expression.After intervention of PI3K inhibitor LY294002,salidroside had no obvious effect on the above indicators,indicating that LY294002 could block the inhibitory effect of salidroside on LPS-induced inflammation in rat brain.Conclusion Salidroside glucoside can reduce the LPS induced neutrophil infiltration,and inhibit the NF-κB nucleoprotein and inflammation through the PI3K/Akt pathway,thus exerting an anti-inflammatory effect.

关 键 词：红景天苷 抗炎 脂多糖 PI3K/AKT NF-ΚB 中性粒细胞 

分 类 号：R-332[医药卫生] R284.1R322.81R364.5R971.1