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

Therapeuitc effect of neurokinin-1 receptor's antagonist on lung injury of acute necrotizing pancreatitis

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 m l。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6 h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 neurokinin-1 receptor （ NK- 1 R） antagonist acute necrotizing pancreatitis （ANP）. Methods 90 adult SD rats, with equal number of male and divided into 3 groups. The rats in group ANP were induced by the retrograde intraductal infusion on the lung injury of female were randomly 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 , Ⅱ epithelium 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.