李凡,谢玮鑫,李展春

• 1:上海交通大学医学院附属仁济医院骨科

摘要(Abstract)：

椎间盘退变是退变性脊柱疾病的关键病因和病理基础,探讨椎间盘退变的病理机制对退变性脊柱疾病的防治具有重要意义。近年来,越来越多的研究表明神经肽Y (neuropeptide Y, NPY)在椎间盘退变的病理机制中发挥重要作用。本文就NPY参与椎间盘退变发病机制的研究进展进行综述,以期为退变性脊柱疾病的防治提供新参考。

关键词(KeyWords)： 椎间盘退变;神经肽Y;发病机制

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上资助项目（编号：81871090,81370976）

作者(Author): 李凡,谢玮鑫,李展春

参考文献(References)：

• [1]Martin BI,Mirza SK,Spina N,et al.Trends in lumbar fusion procedure rates and associated hospital costs for degenerative spinal diseases in the United States,2004 to 2015[J].Spine,2019,44(5):369-376.
• [2]Smith MP,Myren RL,Wood AT,et al.An immunohistochemical study of human thoracic intervertebral discs[R].Federation American Societies Experimental Biology,2009.
• [3]王永刚.NPY和CGRP在人腰椎间盘中的分布与表达及其意义的研究[D].兰州大学,2012.
• [4]韩燚,谢玮鑫,肖洁,等.神经肽Y和受体在腰椎动静力失衡大鼠模型中表达及对痛阈的影响[J].重庆医科大学学报,2019,44(6):689.
• [5]Lee M,Hadi M,Halldén G,et al.Peptide YY and neuropeptide Yinduce villin expression,reduce adhesion,and enhance migration in small intestinal cells through the regulation of CD63,matrix metalloproteinase-3,and Cdc42 activity[J].J Biol Chem,2005,280(1):125-136.
• [6]Park MH,Lee JK,Kim N,et al.Neuropeptide y induces hematopoietic stem/progenitor cell mobilization by regulating matrix metalloproteinase 9 activity through Y1 receptor in osteoblasts[J].Stem Cells,2016,34(8):2145-2156.
• [7]廖乐乐.雷奈酸锶,h EGF,NPY和WISP3对体外人关节软骨细胞的作用[D].中南大学,2010.
• [8]Risbud MV,Shapiro IM.Role of cytokines in intervertebral disc degeneration:pain and disc content[J].Nat Rev Rheumatol,2014,10(1):44.
• [9]Hernanz A,Medina S,De Miguel E,et al.Effect of calcitonin gene-related peptide,neuropeptide Y,substance P,and vasoactive intestinal peptide on interleukin-1β,interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients[J].Regul Pept,2003,115(1):19-24.
• [10]Ferreira R,Xapelli S,Santos T,et al.Neuropeptide Y modulation of interleukin-1β(IL-1β)-induced nitric oxide production in microglia[J].J Biol Chem,2010,285(53):41921-41934.
• [11]ZY,JZ,CY.Ligusticum wallichii extract inhibited the expression of IL-1βafter AMI in rats[J].Evid Based Complement Alternat Med,2014,2014:620359.
• [12]Tang P,Gu JM,Xie ZA,et al.Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NL-RP3 inflammasome signal pathway[J].Free Radic Biol Med,2018,120:368-379.
• [13]Shin MK,Choi B,Kim EY,et al.Elevated pentraxin 3 in obese adipose tissue promotes adipogenic differentiation by activating neuropeptide y signaling[J].Front Immunol,2018,9:1790.
• [14]Zhang F,Zhao X,Shen H,et al.Molecular mechanisms of cell death in intervertebral disc degeneration[J].Int J Mol Med,2016,37(6):1439-1448.
• [15]Wang H,Liu H,Zheng ZM,et al.Role of death receptor,mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc[J].Apoptosis,2011,16(10):990.
• [16]Lu XY,Ding XH,Zhong LJ,et al.Expression and significance of VEGF and p53 in degenerate intervertebral disc tissue[J].Asian Pac J Trop Med,2013,6(1):79-81.
• [17]Sirotkin AV,Kardo?ováD,Alwasel SH,et al.Neuropeptide Y directly affects ovarian cell proliferation and apoptosis[J].Reprod Biol,2015,15(4):257-260.
• [18]Luo G,Xu X,Guo W,et al.Neuropeptide Y damages the integrity of mitochondrial structure and disrupts energy metabolism in cultured neonatal rat cardiomyocytes[J].Peptides,2015,71:162-169.
• [19]Lee DY,Hong SH,Kim B,et al.Neuropeptide Y mitigates ERstress-induced neuronal cell death by activating the PI3K-XBP1pathway[J].Eur J Cell Biol,2018,97(5):339-348.
• [20]Aveleira CA,Botelho M,Carmo-Silva S,et al.Neuropeptide Ystimulates autophagy in hypothalamic neurons[J].Proc Natl Acad Sci U S A,2015,112(13):E1642-1651.
• [21]Zhou JR,Xu Z,Jiang CL.Neuropeptide Y promotes TGF-β1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor[J].Neurosci Bull,2008,24(3):155-159.
• [22]Ouyang ZH,Wang WJ,Yan YG,et al.The PI3K/Akt pathway:a critical player in intervertebral disc degeneration[J].Oncotarget,2017,8(34):57870.
• [23]Chen R,Hao Z,Chen X,et al.Neuropeptide Y enhances proliferation and chondrogenic differentiation of ATDC5 cells[J].Neuropeptides,2020,2020:102022.
• [24]Feng C,Yang M,Lan M,et al.ROS:crucial intermediators in the pathogenesis of intervertebral disc degeneration[J].Oxid Med Cell Longev,2017,2017:5601593.
• [25]Bedoui S,Von H?rsten S,Gebhardt T.A role for neuropeptide Y(NPY) in phagocytosis:implications for innate and adaptive immunity[J].Peptides,2007,28(2):373-376.
• [26]Balasubramaniam A,Grupp I,Matlib M,et al.Comparison of the effects of neuropeptide Y(NPY) and 4-norleucine-NPY on isolated perfused rat hearts;effects of NPY on atrial and ventricular strips of rat heart and on rabbit heart mitochondria[J].Regul Pept,1988,21(3-4):289-299.
• [27]Park S,Fujishita C,Komatsu T,et al.NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism[J].FASEB J,2014,28(12):5337-5348.
• [28]Lu XY,Ding XH,Zhong LJ,et al.Expression and significance of VEGF and p53 in degenerate intervertebral disc tissue[J].Asian Pac J Trop Med,2013,6(1):79-81.
• [29]Zukowska-Grojec Z,Karwatowska-Prokopczuk E,Rose W,et al.Neuropeptide Y:a novel angiogenic factor from the sympathetic nerves and endothelium[J].Circ Res,1998,83(2):187-195.
• [30]Lee EW,Michalkiewicz M,Kitlinska J,et al.Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles[J].J Clin Invest,2003,111(12):1853-1862.
• [31]Robich MP,Matyal R,Chu LM,et al.Effects of neuropeptide Y on collateral development in a swine model of chronic myocardial ischemia[J].J Mol Cell Cardiol,2010,49(6):1022-1030.
• [32]Alasvand M,Javanmard SH,Rashidi B,et al.Myocardial capillary density after neuropeptide Y antagonist administration in normal and high-fat diet C57BL6 mice[J].Adv Biomed Res,2016,5:1-9.
• [33]Liu Z-H,Sun Z,Wang H-Q,et al.Fas L expression on human nucleus pulposus cells contributes to the immune privilege of intervertebral disc by interacting with immunocytes[J].Int J Med Sci,2013,10(8):1053.
• [34]Wheway J,Mackay CR,Newton RA,et al.A fundamental bimodal role for neuropeptide Y1 receptor in the immune system[J].J Exper Med,2005,202(11):1527-1538.