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麻黄-杏仁药对对呼吸中枢的平喘作用及机制
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| 篇名： | 麻黄-杏仁药对对呼吸中枢的平喘作用及机制 |
| TITLE： | Antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center |
| 摘要： | 目的 初步探讨麻黄-杏仁药对对呼吸中枢的平喘作用及机制。方法雄性SD大鼠随机分为空白组、模型组、地塞米松组（阳性对照）以及麻黄-杏仁2∶1、1∶1、1∶2组。各组大鼠灌胃不同配比药对水煎液[均为18g（生药）/kg]/地塞米松混悬液（0.5mg/kg）/等体积生理盐水，每日灌胃2次，连续7d。于末次给药40min后，取含药脑脊液测定大鼠入脑有效成分的含量；于末次给药1.5h后，通过脑立体定位仪定位孤束核，用10μL微量进样器以恒速1μL/min将磷酸组胺注入孤束核区域（体积1μL）模拟大鼠呼吸中枢兴奋状态，空白组注射生理盐水。检测延髓部脑组织中神经递质[神经生长因子（NGF）、P物质（SP）、去甲肾上腺素（NA）、5-羟色胺（5-HT）、乙酰胆碱（Ach）]的含量；检测延髓部脑组织中神经激肽1受体（NK-1R）、p38促分裂原活化的蛋白激酶（MAPK）、c-fosmRNA表达，以及孤束核区域NK-1R、p38MAPK、c-fos蛋白表达。结果麻黄-杏仁药对入脑的主要有效成分为麻黄碱、伪麻黄碱、甲基麻黄碱。与空白组相比，模型组大鼠NGF、SP、NA、5-HT、Ach含量，以及NK-1R、p38MAPK、c-fosmRNA和蛋白的相对表达水平均显著升高（P＜0.01）；与模型组相比，麻黄-杏仁药对不同配比组均能显著降低各神经递质含量，以及NK-1R、p38MAPK、c-fosmRNA和蛋白的相对表达水平（P＜0.01），其中以质量比2∶1与1∶1配比的药对效果相对较好。结论麻黄生物碱类为麻黄-杏仁药对影响呼吸中枢功能的主要有效成分；麻黄占比较大的配比组效应较强；麻黄-杏仁药对可通过下调孤束核NK-1R/MAPK/c-fos通路表达，减少NGF、SP等神经递质异常释放，降低呼吸中枢兴奋性。 |
| ABSTRACT： | OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP. |
| 期刊： | 2026年第37卷第07期 |
| 作者： | 田佳玉；杨添翼；谢金根；陈林林；饶倩；肖雄；侯永春；李文宏 |
| AUTHORS： | TIAN Jiayu，YANG Tianyi，XIE Jingen，CHEN Linlin，RAO Qian，XIAO Xiong，HOU Yongchun，LI Wenhong |
| 关键字： | 麻黄-杏仁药对；平喘；呼吸中枢；脑立体定位；孤束核；NK-1R/MAPK/c-fos通路 |
| KEYWORDS： | Ephedrae Herba-Armeniacae Semen Amarum herb pair； antiasthmatic； respiratory center； brain stereotaxis； |
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