摘要
目的建立大鼠急性咽炎模型并结合网络药理学,基于核因子-κB(nuclear factor-κB,NF-κB)/信号传导及转录激活因子(signal transducer and activator of transcription,STAT)信号通路探讨朱砂根Ardisia crenata干预大鼠急性咽炎的作用机制。方法通过网络药理学方法预测朱砂根干预急性咽炎的靶点,构建活性成分-靶点、靶点-通路网络。构建急性咽炎大鼠模型,检测大鼠血清中白细胞介素-6(interleukin-6,IL-6)、前列腺素E2(prostaglandin E2,PEG2)和IL-10水平;采用qRT-PCR检测大鼠咽部组织中半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)、Caspase-7、Caspase-8、蛋白酪氨酸性磷酸非受体型11(protein tyrosine phosphatase nonreceptor 11,PTPN11)、蛋白激酶B1(protein kinase B1,AKT1)和Janus激酶2(Janus kinase 2,JAK2)mRNA表达;采用Western blotting检测大鼠咽部组织中AKT1、JAK2和Caspase-8蛋白表达。结果网络药理学研究显示,朱砂根主要活性成分与急性咽炎有168个交集靶点,主要作用于NF-κB/STAT信号通路。与模型组比较,朱砂根组大鼠血清中IL-6和PEG_(2)水平明显降低(P<0.01),IL-10水平显著升高(P<0.05、0.01);咽部组织Caspase-3、Caspase-7、Caspase-8、PTPN11、AKT1和JAK2 mRNA表达水平均显著降低(P<0.05、0.01),Caspase-8、AKT1和JAK2蛋白表达水平均显著降低(P<0.05、0.01)。结论朱砂根中的活性成分可能通过调控NF-κB/STAT信号通路,干预炎症反应并加速巨噬细胞分化、凋亡,从而治疗急性咽炎。
Objective To explore the mechanism of Ardisia crenata on rats with acute pharyngitis based on nuclear factor kappa-B(NF-κB)/signal transducer and activator of transcription(STAT)signaling pathway by establishing acute pharyngitis rats model combined with network pharmacology,.Methods The target of A.crenata intervention in acute pharyngitis was predicted by network pharmacology,and networks of active ingredient-target and target-pathway were constructed;Rat model of acute pharyngitis was constructed,levels of interleukin-6(IL-6),prostaglandin E2(PEG2)and IL-10 in serum of rats were detected;qRT-PCR was used to detect cystein-asparate protease-3(Caspase-3),Caspase-7,Caspase-8,protein tyrosine phosphatase nonreceptor 11(PTPN11),protein kinase B1(AKT1)and Janus kinase 2(JAK2)mRNA expressions in pharyngeal tissue of rats;Western blotting was used to detect AKT1,JAK2 and Caspase-8 protein expression in pharyngeal tissue of rats.Results The network pharmacology showed that main active components of A.crenata had 168 intersecting targets with acute pharyngitis,mainly acting on NF-κB/STAT signaling pathway.Compared with model group,levels of IL-6 and PEG2 in serum of rats in A.crenata group were significantly decreased(P<0.01),and IL-10 level was significantly increased(P<0.05,0.01),mRNA expression levels of Caspase-3,Caspase-7,Caspase-8,PTPN11,AKT1 and JAK2 were significantly decreased(P<0.05,0.01),protein expressions of Caspase-8,AKT1 and JAK2 were significantly decreased(P<0.05,0.01).Conclusion The active components in A.crenata may regulate NF-κB/STAT signaling pathway,intervene in inflammatory response and accelerate the differentiation and apoptosis of macrophages,thereby treating acute pharyngitis.
作者
权伟
刘畅
周英
何倩倩
石洋
党兆岩
刘雄利
QUAN Wei;LIU Chang;ZHOU Ying;HE Qian-qian;SHI Yang;DANG Zhao-yan;LIU Xiong-li(Research Center for Application and Development of Medicine and Food Dual-use Resources,School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;National and Local Joint Engineering Research Center of Southwest Medicinal and Edible Resources Development and Utilization Technology,Guizhou University,Guiyang 550025,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第19期6083-6092,共10页
Chinese Traditional and Herbal Drugs
基金
国家重点研发计划项目(2018YFC1708100)
贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY-2021-098)
贵州中医药大学2021年度科研创新和探索专项(2018YFC170810201,2018YFC170810204)
贵州中医药大学本科教学工程建设项目(贵中医教学工程合字[2021]12号)。
关键词
朱砂根
网络药理学
核因子-κB/信号传导及转录激活因子信号通路
急性咽炎
巨噬细胞
Ardisia crenata Sims
network pharmacology
nuclear factor-κB/signal transducer and activator of transcription signaling pathway
acute pharyngitis
macrophage
