AbMole小讲堂丨Substance P（Neurokinin P）：一个参与痛觉、炎症与组织修复的多功能神经肽

Substance P（Neurokinin P，AbMole，M9080）是一种11氨基酸的神经肽，属于速激肽家族，主要通过激活神经激肽1受体（NK1R）介导信号传导，涉及痛觉传递、炎症调节和细胞间通信等细胞活动，还能调节钙离子流量、ERK磷酸化和NF-κB活化等过程[1]。在细胞实验方面，Substance P（CAS No.：33507-63-0）在H9C2大鼠心肌细胞中以1-10 nM浓度预处理后，可增加细胞中磷酸化Akt（p-Akt）的水平并抑制缺氧/再氧合诱导的细胞凋亡[2]；Substance P在皮肤肥大细胞中，可诱导浓度依赖性的组胺释放，而阻断NK1R后可抑制此效应[3]；Substance P还在SiHa宫颈癌细胞中，以浓度依赖方式促进增殖和侵袭，并激活ERK1/2磷酸化[4]；Substance P在兔成骨细胞模型中，以1 μM的浓度有效促进成骨分化和组织修复[5]；Substance P（Neurokinin P）还可以用于神经系统和疼痛相关的研究，例如在ICR小鼠神经性疼痛模型中的研究显示，静脉注射Neurokinin P（1 nmol/kg）可抑制疼痛相关炎症和疼痛因子的活性[6]；Substance P在豚鼠和人类迷走神经中，引起去极化，而Aprepitant 可抑制上述效应[7]；Substance P还在猪急性心肌梗塞模型中，通过静脉注射（5 nmol/kg）后提供心脏保护作用[8]。上述这些研究揭示了Substance P在细胞信号传导和动物模型中的多功能性，为理解其生物学作用提供了基础。

参考文献及鸣谢

[1] Spitsin, S.; Pappa, V.; Douglas, S. D. Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling.Journal of leukocyte biology2018.

[2] Xu, Y.; Gu, Q.; Tang, J.; et al. Substance P Attenuates Hypoxia/Reoxygenation-Induced Apoptosis via the Akt Signalling Pathway and the NK1-Receptor in H9C2Cells.Heart, lung & circulation2018,27(12), 1498-1506.

[3] Hermans, M. A. W.; Schrijver, B.; van Holten-Neelen, C.; et al. The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology2018,48(11), 1412-1420.

[4] Wang, Y.; Yuan, S.; Ma, J.; et al. Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells <em>in vitro</em>.European journal of histochemistry : EJH2023,67(3).

[5] Chen, J.; Liu, W.; Zhao, J.; et al. Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits.Biotechnology letters2017,39(3), 465-472.

[6] Chung, E.; Yoon, T. G.; Kim, S.; et al. Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors.Biomolecules & therapeutics2017,25(3), 259-265.

[7] Smith, J. A.; Harle, A.; Dockry, R.; et al. Aprepitant for Cough in Lung Cancer. A Randomized Placebo-controlled Trial and Mechanistic Insights.American journal of respiratory and critical care medicine2021,203(6), 737-745.

[8] Sim, D. S.; Kim, W.; Lee, K. H.; et al. Cardioprotective effect of substance P in a porcine model of acute myocardial infarction.International journal of cardiology2018,271, 228-232.