芥子碱硫氰酸盐可溶性微针穴位给药抗支气管哮喘的药效学研究  

Pharmacodynamic study of sinapine thiocyanate dissoluble microneedle for acupoint administration against bronchial asthma

作　　者：石佳楠 宋信莉 刘兴德 陈欢欢 杨小双 杨胜磊 沈丽 万开龙 SHI Jianan;SONG Xinli;LIU Xingde;CHEN Huanhuan;YANG Xiaoshuang;YANG Shenglei;SHEN Li;WAN Kailong(School of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Engineering Technology Research Center for Miao Medicine/Guizhou Engineering Technology Research Center for Traditional Chinese Medicine Processing and Preparation,Guiyang 550025,China)

机构地区：[1]贵州中医药大学药学院/国家苗药工程技术研究中心/贵州中药炮制与制剂工程技术研究中心,贵阳550025

出　　处：《中国药房》2022年第22期2728-2732,共5页China Pharmacy

基　　金：贵州省科技计划项目(No.黔科合基础-ZK〔2021〕一般530);贵州省特色功能食品与中药制剂开发集成攻关项目(No.黔教合KY字〔2020〕006);贵州中医药大学药用高分子材料研究中心项目(No.贵中医党办发〔2019〕70号);贵州中医药大学博士启动基金(No.贵中医博士启动〔2021〕14号);贵州省一流学科建设项目(No.GNYL〔2017〕008号);贵州省药物新剂型新工艺科技创新人才团队项目(No.黔科合平台人才〔2017〕5655)。

摘　　要：目的研究芥子碱硫氰酸盐可溶性微针(ST-DMN)穴位给药抗支气管哮喘(BA)的疗效。方法采用网络药理学方法和分子对接技术筛选芥子碱硫氰酸盐(ST)抗BA的核心靶点,并针对排名前3位的核心靶点进行药效学研究。首先制备ST-DMN(ST载药量为1 mg/片),再将30只大鼠分为空白对照组、模型对照组、空白微针组、白芥子散敷贴组(阳性对照组)和ST-DMN组,除空白对照组外,其余各组大鼠采用10%卵清蛋白(含氢氧化铝佐剂)致敏和1%卵清蛋白雾化激发以复制BA模型。造模成功后,空白对照组大鼠不处理,模型对照组大鼠于肺俞穴、大椎穴涂抹生理盐水,空白微针组、白芥子散敷贴组、ST-DMN组大鼠分别于相同穴位给予空白微针、白芥子散(敷贴,1.5 g)、ST-DMN(2个穴位共给予3片)处理,每天1次,连续28 d。给药结束后,观察大鼠一般症状并测定体质量,观察大鼠肺组织的病理学形态变化,检测大鼠血清、支气管肺泡灌洗液(BALF)、肺组织中前列腺素内过氧化物合酶2(PTGS2)、基质金属蛋白酶9(MMP-9)、白细胞介素2(IL-2)的水平。结果网络药理学和分子对接结果显示,ST抗BA的关键靶点有PTGS2、MMP-9、IL-2、表皮生长因子受体、热休克蛋白90AA1等。药效实验结果显示,与模型对照组比较,ST-DMN组大鼠咳嗽减轻,毛色恢复,行为灵敏,呼吸平稳,体质量增加;肺组织结构、肺泡上皮细胞、肺间质炎症细胞浸润等病理变化均得到不同程度的改善;血清、BALF、肺组织中PTGS2、MMP-9、IL-2水平均明显降低(P<0.05或P<0.01)。结论ST-DMN穴位给药抗BA的效果良好,其作用机制可能与下调血清、BALF、肺组织中PTGS2、MMP-9、IL-2水平有关。OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle(ST-DMN)for acupoint administration against bronchial asthma(BA).METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate(ST)against BA,and the pharmacodynamics of the top 3 core targets was studied.Firstly,ST-DMN was prepared(drug loading of ST was 1 mg/tablet);secondly,30 rats were divided into blank control group,model control group,blank microneedle group,Sinapine powder plaster group(positive control group)and ST-DMN group.Except for the blank control group,rats of other groups were sensitized with 10%ovalbumin(containing aluminum hydroxide adjuvant)and nebulized with 1%ovalbumin to induce the BA model.After modeling,blank control group did not receive any intervention;normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group,while the blank microneedle group,Sinapine powder plaster group and ST-DMN group were given blank microneedle,Sinapis alba powder(plaster,1.5 g)and ST-DMN(3 tablets at 2 acupoints)at same acupoint,once a day,for 28 consecutive days.After administration,the general symptoms were observed and the body mass of the rats was measured.The pathological changes of lung tissues in rats was observed;the levels of prostaglandin endoperoxide synthase 2(PTGS2),matrix metalloproteinase-9(MMP-9)and interleukin-2(IL-2)in serum,bronchoalveolar lavage fluid(BALF)and lung tissues were determined.RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2,MMP-9,IL-2,epidermal growth factor receptor,heat shock protein90AA1,etc.Pharmacodynamic experiments showed that compared with model control group,relieved cough,restored hair color,sensitive behavior,stable respiration and increased body weight were all found in ST-DMN group;the histopathological changes as the structure of lung tissue,infiltration of alveolar epithelial cells and pulmonary

关 键 词：芥子碱硫氰酸盐 可溶性微针 穴位给药 支气管哮喘 作用靶点 药效学 

分 类 号：R965[医药卫生—药理学]