P物质受体拮抗剂对急性坏死性胰腺炎时肺损伤保护作用的实验研究-东南大学学报医学版

P物质受体拮抗剂对急性坏死性胰腺炎时肺损伤保护作用的实验研究

单位：1.东南大学附属中大医院,普外科,江苏,南京,210009； 2.扬州大学,江苏,扬州,225000

分类号：R576, R-33

出版年·卷·期（页码）：2007·26·第三期（174-177）

摘要：

目的:探讨神经激肽-1受体(NK-1R) 拮抗剂对急性坏死性胰腺炎(ANP)大鼠肺损伤的作用,了解ANP时阻断该受体对肺损害是否具有保护作用.方法:90只健康成年SD大鼠随机分为正常对照组、ANP组和拮抗剂组各30只.正常对照组开腹后只翻动胰腺,ANP组和拮抗剂组胆胰管恒速逆行注射5%牛磺胆酸钠,制成ANP大鼠模型.拮抗剂组在制模成功后经尾静脉注射NK-1R拮抗剂spantide(0.001 25%) 0.5 ml.检测不同时间点肺髓过氧化物酶(MPO)活性和肺毛细血管通透性(LCP)的变化.应用免疫组织化学方法进行NK-1R的组织学定位.结果:ANP组6h后肺组织MPO活性和LCP即明显高于正常对照组,并且持续升高(P＜0.01).与正常对照组的各个时间点相比,拮抗剂组肺组织MPO活性和LCP没有明显变化(P＞0.05).免疫组化检查显示,NK-1R的表达主要位于肺泡隔血管内皮细胞表面及部分肺泡Ⅰ、Ⅱ型上皮细胞表面等处.结论:ANP 时,P物质通过与NK-1R结合发挥作用,NK-1R拮抗剂阻断了P物质的作用路径,对ANP肺损伤起到一定的治疗作用.

Objective To investigate the effect of neurokinin1 receptor(NK-1R) antagonist on the lung injury of acute necrotizing pancreatitis(ANP).Methods 90 adult SD rats,with equal number of male and female were randomly divided into 3 groups.The rats in group ANP were induced by the retrograde intraductal infusion of 5% sodium taurocholate(0.01ml·kg-1 min-1).In the antagonist group,0.5 ml spantide(0.001 25%) was injected after ANP model was established.And the rats in normal control group received laparotomy only.The accumulation of polymorphonuclear leukocytes in lung tissues was measured by the myeloperoxidase(MPO) assay.Lung endothelial barrier destruction was assessed by lung capillary permeability(LCP).Immunohistochemistry was used to localize the expression site of NK-1R.Results:The level of MPO and LCP in ANP group,increasing along with time,was significantly higher than that of normal control group(P<0.01),respectively.Whereas the level of MPO and LCP in antagonist group was not significantly higher than that of normal control group(P>0.05).Immunohistochemistry revealed that moderate to strong NK1R immunoreactivity was localized to alveolar membrane,Ⅰ,Ⅱepithelium and polymorphonuclear leukocytes in the lung of ANP.Conclusion In ANP,neurokinin-1 receptor antagonist(spantide) combined with substance P,exerting a beneficial effect on acute lung injury through blocking substance P,has a therapeutic effect on the disease.

参考文献：

[1] YADAV D, LOWENFELS A B. Trends in the epidemiology of the first attack of acute pancreatitis:a systematic review. 2006(4). doi:10.1097/01.mpa.0000236733.31617.52
[2] NOBLE M D, ROMAC J, WANG Y. Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats. 2006(1)
[3] 宿士智, 石欣, 高乃荣. 大鼠急性坏死性胰腺炎时P物质在肠壁上的表达及其与肠黏膜通透性的关系. 东南大学学报(医学版)2005(6). doi:10.3969/j.issn.1671-6264.2005.06.001
[4] 石欣, 高乃荣, 尹勇. 神经激肽-1受体在急性坏死性胰腺炎肺损害中的作用. 中国危重病急救医学2003(7)
[5] McDONALD D M, THURSTON G, BALUK P. Endothelial gaps as sites for plasma leakage in inflammation. 1999(1). doi:10.1080/713773924
[6] BHATIA M, SALUJA A K, HOFBAUER B. Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. 1998(8). doi:10.1073/pnas.95.8.4760
[7] GRADY E F, YOSHIMI S K, MAA J. Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. 2000(3). doi:10.1038/sj.bjp.0703343
[8] MAA J, GRADY E F, YOSHIMI S K. Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice. 2000(2). doi:10.1067/msy.2000.107378

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