Substance P作為參與痛覺、炎癥與組織修復(fù)的多功能神經(jīng)肽的作用機(jī)制

Substance P（Neurokinin P，AbMole，M9080）是一種11氨基酸的神經(jīng)肽，屬于速激肽家族，主要通過激活神經(jīng)激肽1受體（NK1R）介導(dǎo)信號(hào)傳導(dǎo)，涉及痛覺傳遞、炎癥調(diào)節(jié)和細(xì)胞間通信等細(xì)胞活動(dòng)，還能調(diào)節(jié)鈣離子流量、ERK磷酸化和NF-κB活化等過程[1]。在細(xì)胞實(shí)驗(yàn)方面，Substance P（CAS No.：33507-63-0）在H9C2大鼠心肌細(xì)胞中以1-10 nM濃度預(yù)處理后，可增加細(xì)胞中磷酸化Akt（p-Akt）的水平并抑制缺氧/再氧合誘導(dǎo)的細(xì)胞凋亡[2]；Substance P在皮膚肥大細(xì)胞中，可誘導(dǎo)濃度依賴性的組胺釋放，而阻斷NK1R后可抑制此效應(yīng)[3]；Substance P還在SiHa宮頸癌細(xì)胞中，以濃度依賴方式促進(jìn)增殖和侵襲，并激活ERK1/2磷酸化[4]；Substance P在兔成骨細(xì)胞模型中，以1 μM的濃度有效促進(jìn)成骨分化和組織修復(fù)[5]；

Substance P（Neurokinin P）還可以用于神經(jīng)系統(tǒng)和疼痛相關(guān)的研究，例如在ICR小鼠神經(jīng)性疼痛模型中的研究顯示，靜脈注射Neurokinin P（1 nmol/kg）可抑制疼痛相關(guān)炎癥和疼痛因子的活性[6]；Substance P在豚鼠和人類迷走神經(jīng)中，引起去極化，而Aprepitant 可抑制上述效應(yīng)[7]；Substance P還在豬急性心肌梗塞模型中，通過靜脈注射（5 nmol/kg）后提供心臟保護(hù)作用[8]。上述這些研究揭示了Substance P在細(xì)胞信號(hào)傳導(dǎo)和動(dòng)物模型中的多功能性，為理解其生物學(xué)作用提供了基礎(chǔ)。

參考文獻(xiàn)及鳴謝
[1] Spitsin, S.; Pappa, V.; Douglas, S. D. Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling. Journal of leukocyte biology 2018.
[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 & circulation 2018, 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 Immunology 2018, 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 in vitro. European journal of histochemistry : EJH 2023, 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 letters 2017, 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 & therapeutics 2017, 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 medicine 2021, 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 cardiology 2018, 271, 228-232.