中国药物警戒 ›› 2025, Vol. 22 ›› Issue (6): 608-613.
DOI: 10.19803/j.1672-8629.20241025

• 基础与临床研究 • 上一篇    下一篇

芫根中青藤碱抗低氧肺血管损伤作用研究

林琳1,2, 杨婷羽1,2, 高熔2,3, 马增春2, 沈歆2#, 高月1,2*   

  1. 1天津中医药大学研究生学院,天津 301617;
    2军事科学院军事医学研究院,北京 100850;
    3广东药科大学药学院,广东 广州 510006
  • 收稿日期:2024-12-18 发布日期:2025-06-18
  • 通讯作者: *高月,女,研究员,博导,中药药理学。E-mail: gaoyue@bmi.ac.cn;#为共同通信作者。
  • 作者简介:林琳,女,在读硕士,中药学。
  • 基金资助:
    国家自然科学基金资助项目（82304867）

Effects of Sinomenine in Brassica rapa L. against Hypoxic Pulmonary Vascular Injury

LIN Lin1,2, YANG Tingyu1,2, GAO Rong2,3, MA Zengchun2, SHEN Xin2#, GAO Yue1,2*   

  1. 1Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;
    2Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;
    3College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou Guangdong 510006, China
  • Received:2024-12-18 Published:2025-06-18

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摘要： 目的 建立准确测定远志药材和饮片中4种黄曲霉毒素的高效液相色谱（HPLC）方法。方法 采用Ultimate XB-C18色谱柱（4.6 mm×150 mm,5μm）,以甲醇-乙腈-水（22∶10∶68）为流动相,流速0.7 mL·min-1,柱温40℃,荧光检测器（λex=360 nm,λex=450 nm）检测,进样量10μL。对比不同提取方法与不同品牌免疫亲和柱的提取净化效果,优化前处理过程,考察基质效应对检测结果的影响,并对28批远志药材及饮片的黄曲霉毒素含量进行测定。结果 方法学考察结果符合中药质量分析要求。黄曲霉毒素G2（AFG2）、黄曲霉毒素B2（AFB2）在0.000 075~0.075 μg·mL-1,黄曲霉毒素G1（AFG1）、黄曲霉毒素B1（AFB1）在0.000 25~0.25 μg·mL-1内线性关系良好,相关系数均为0.999 9,基质效应为94.49%~103.51%,可视为远志基质对黄曲霉毒素的测定无影响。在低、中、高浓度下AFG2、AFG1、AFB2和AFB1的平均回收率分别为78.98%~93.51%、81.88%~100.74%、82.19%~116.12%,相对标准偏差（RSD）介于1.1%~6.6%。针对远志品种更适宜使用均质器提取黄曲霉毒素,以及免疫亲和柱富集。28批远志样品中,有2批药材不合格,其余26批药材与饮片均符合药典标准。黄曲霉毒素总量最高达313.63μg·kg-1,AFB1的含量最高达143.27μg·kg-1。结论 建立了远志药材中4种黄曲霉毒素同步测定的简便、可靠新方法,完善了已有检测方法,揭示了远志普遍存在黄曲霉毒素污染风险,为提升远志药材质量提供参考。

关键词: 远志, 黄曲霉毒素, 高效液相色谱-荧光检测联用, 基质效应

Abstract: Objective To observe the effects of interventions involving sinomenine in Brassica rapa L. on pulmonary vascular remodeling and pulmonary function in mice with hypoxic pulmonary vascular injury (HPVI). Methods Forty-eight mice were randomly divided into six groups: blank control group (Con), model group (Mod), sinomenine intervention low-, medium- and high-dose groups (L, M, H, at 50, 100, 150 mg·kg-1 respectively), and dexamethasone (Dex) administration group. When hypoxia was terminated, routine blood tests, bronchoalveolar lavage fluid (BALF) examination, small animal ultrasound, blood oxygen saturation (SaO2) measurement, blood biochemistry analysis, pulmonary tissue pathology examination, and immunohistochemistry were conducted. Western blot (WB) was used to detect the protein expressions of HIF-1α, VEGFA, Ang2, IL-1β, and NF-κB to find out about the mechanism of action. High-resolution mass spectrometry (HRMS) technology was employed for quantitative analysis of sinomenine in Brassica rapa L. Results The content of sinomenine in a 1 g·mL-1 aqueous extract sample of Brassica rapa L. was 3.558 mg·mL-1. Sinomenine reduced the numbers of such inflammatory cells as WBCs, NEUTs, and lymphocytes in the serum of HPVI mice. It could significantly lower the cell count in the alveolar lavage fluid and the levels of ALP and LDH. It enhanced the cardiopulmonary function and oxygen saturation of mice, but decreased the frequency of respiration. Furthermore, sinomenine mitigated pathological injury in lung tissues, and significantly reduced the percentage of the area and thickness of the vascular wall. Compared with the model group, sinomenine interventions significantly lowered the protein expression levels of HIF-1α, Ang2, VEGFA, and IL-1β, as well as NF-κB in lung tissues of HPVI mice. Conclusion Sinomenine interventions can effectively inhibit vascular remodeling in HPVI mice, especially in the medium dose group. Sinomenine can regulate vascular homeostasis, improve vascular permeability, enhance cardiopulmonary function, facilitate oxygen uptake and transport, and induce vascular normalization by reducing the expressions of angiogenic factors in lung tissues of mice.

Key words: Sinomenine, Brassica rapa L., Hypoxic Pulmonary Vascular Injury, Vascular Remodeling, Mice

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