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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
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| 篇名： | 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 |
| TITLE： | Pharmacodynamic study of sinapine thiocyanate dissoluble microneedle for acupoint administration against bronchial asthma |
| 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1mg/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，1.5g）、ST-DMN（2个穴位共给予3片）处理，每天1次，连续28d。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。 |
| ABSTRACT： | 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.pathological changes of lung tissues in rats was observed； the levels of prostaglandin endoperoxide synthase 2 （PTGS2）， GNYL 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 interstitial inflammatory cells were improved to different extent； the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good， the mechanism of which may be associated with decreasing the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue. |
| 期刊： | 2022年第33卷第22期 |
| 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 |
| AUTHORS： | SHI Jianan， SONG Xinli，LIU Xingde，CHEN Huanhuan，YANG Xiaoshuang，YANG Shenglei，SHEN Li，WAN Kailong |
| 关键字： | 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 |
| KEYWORDS： | sinapine thiocyanate； dissoluble microneedle； acupoint administration； bronchial asthma； target； |
| 阅读数： | 190 次 |
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