速激肽NK-1受体拮抗剂SR-140333对抗原引起致敏大鼠气道高反应性的影响  

EFFECT OF SR 140333, A TACHYKININ NK 1 ANTAGONIST, ON ANTIGEN INDUCED AIRWAY HYPERRESPONSIVENESS IN SENSITIZED RATS

作　　者：张纬萍[1] 赵孟辉[1] 田炯[1] 俞月萍 陈积愫[1] 魏尔清[1] 

机构地区：[1]浙江医科大学神经生物学实验室

出　　处：《药学学报》1997年第8期569-572,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金;国家教委留学回国人员科技资助

摘　　要：为观察速激肽ＮＫ１受体拮抗剂ＳＲ１４０３３３对抗原攻击引起的致敏大鼠气道高反应性的影响，测定了致敏大鼠在抗原攻击前后的基础呼吸频率，对ＭＣｈ的反应性及支气管肺泡灌洗液中的白细胞数量。实验结果显示，致敏大鼠吸入ＯＡ后６ｈ基础呼吸频率增加，并显著增加乙酰甲胆碱（ＭＣｈ）的反应性、ＭＣｈ的－ｌｏｇＰＣ３０值和支气管肺泡灌洗液中的白细胞数量。ｉｐ速激肽ＮＫ１受体拮抗剂ＳＲ１４０３３３（０１ｍｇ·ｋｇ－１）或地塞米松（０５ｍｇ·ｋｇ－１），可明显抑制上述反应，小剂量ＳＲ１４０３３３（００１ｍｇ·ｋｇ－１）仅有部分抑制作用。结果提示抗原攻击可引起致敏大鼠气道高反应性和气道炎症。In the present study, the effects of SR 140333, {( S ) 1 (2 [3,4 dichlorophenyl) 1 (3 isopropoxyphenylacetyl)piperidin 3yl]ethyl) 4 phenyl 1 azoniabicyclooctane·chloride}, a nonpeptide antagonist for tachykinin NK 1 receptor, on the antigen induced airway response to methacholine (MCh) aerosol and airway inflammation in sensitized SD rats were investigated. The baseline respiratory frequencies, tachypnea response to methacholine(MCh), the -log PC 30 values of MCh and the leukocyte counts in bronchoalveolar lavage significantly increased after inhalation of 1% oval albumin(OA) aerosol. SR 140333 (152 nmol·kg -1 , ip) or dexamethasone(368 nmol·kg -1 , ip), bid×3 d inhibited these responses. SR 140333 at a low dose of 0 01 mg·kg -1 showed an incomplete inhibition. From these results, we conclude that antigen challenge causes airway hyperresponsiveness and airway inflammation and that tachykinin NK 1 receptor antagonist inhibits these responses.

关 键 词：气道高反应性 速激肽受体 拮抗剂 气道炎症 

分 类 号：R974[医药卫生—药品] R560.5[医药卫生—药学]