一氧化氮在P物质诱导BALB／c小鼠搔抓反应中的作用  

Effect of nitric oxide on substance P-induced scratching response in BALB/c mice

作　　者：杨艳平[1] 郑双进[1] 陈蕾[1] 樊翌明[1] 

机构地区：[1]广东医学院附属医院皮肤科,湛江524001

出　　处：《中华皮肤科杂志》2009年第12期843-845,共3页Chinese Journal of Dermatology

基　　金：广东省自然科学基金（7301533）

摘　　要：目的探讨一氧化氮（NO）在P物质诱导小鼠搔抓反应中的作用。方法40只BALB／c小鼠随机分为5组，颈背部皮内注射不同剂量P物质（20～160nmol／N位）建立BALB／c小鼠急性瘙痒模型。另取40只小鼠随机分为5组，分别在颈背部皮内注射生理氯化钠溶液、L-精氨酸、spantide、L—NAME、氨基胍，10min后皮内注射P物质（80nmol／部位），观察这些试剂对P物质诱导小鼠搔抓反应的影响，并用免疫组化和硝酸还原酶法分别检测注射部位皮肤中一氧化氮合酶（iNOS）、NO表达。结果皮内注射生理氯化钠溶液和20、40、80、160nmol／部位P物质引起小鼠1h内搔抓次数分别为4．38±4．07、5．38±3．78、12．75±6．52、23．50±7．84、42．38±15．84；与生理氯化钠溶液组相比，40～160nmol/部位P物质可使小鼠出现剂量依赖性搔抓反应（P〈0．01～0．05）。P物质组、L-精氨酸组、spantide组、L—NAME组和氨基胍组小鼠1h内搔抓次数分别为67．13±32．79、70．75±34．80、10．75±8．14、29．00±21．19、35．38±22．83；与P物质组相比，spantide、L—NAME、氨基胍可明显减少P物质诱导的小鼠搔抓次数（P〈0．01～0．05），但L-精氨酸无明显影响（P〉0．05）。与P物质组比较，spantide、L—NAME、氨基胍可下调皮肤中iNOS表达和NO水平（P〈0．01～0．05），而L-精氨酸无明显作用（P〉0．05）。结论P物质可能通过激活皮肤中神经激肽1受体来促进NO合成，从而引起BALB／c小鼠搔抓反应.Objective To investigate the effect of nitric oxide （NO） on the scratching behavior evoked by substance P （SP） in mice. Methods Forty BALB/c mice were randomly divided into 5 groups to receive intradermal injection of different doses of SP （0, 20, 40, 80, 160 nmol/site） into the rostral part of the back to establish the acute itch model. Another 40 mice were randomly allocated to model, spantide, L-arginine, L-NAME and aminognanidine groups injected intracutaneously with normal saline （NS）, spantide, L-arginine, L-NAME and aminoguanidine, respectively, 10 minutes before SP （80 nmol/site） injection. Subsequently, the scratching behavior was observed, iNOS expression and NO level in the injected skin were detected by immunohistoehemical staining and nitrate reductase assay, respectively. Results The scratching bouts per hour induced by intradermal NS and SP of 20, 40, 80 and 160 nmol/site were 4.38 ± 4.07, 5.38 ± 3.78, 12.75±6.52, 23.50 ± 7.84 and 42.38 ± 15.84, respectively, and only SP at higher doses （40 - 160 nmol/site） elicited a dose-dependent scratching response in mice （P 〈 0.01 or 0.05） compared with NS. The scratches over 1 hour in SP, L-arginine, spantide, L-NAME and aminoguanidine group were 67.13 ±32.79, 70.75±34.80, 10.75± 8.14, 29.00 ± 21.19 and 35.38 ± 22.83, respectively; of them, pretreatment with spantide, L-NAME and aminognanidine significantly inhibited SP-induced scratching （P 〈 0.01 or 0.05）, but L-argi- nine showed no inhibitory effect （P 〉 0.05 ）. Compared with SP, the pretreatment with spantide, L-NAME and aminoguanidine significantly downregulated the iNOS expression and NO content （P 〈 0.01 or 0.05 ） in the injected skin other than L-arginine （P 〉 0.05 ）. Conclusion Intradermal SP could increase NO synthesis by neurokinin 1 receptor activation, resulting in the scratching behavior in BALB/c mice.

关 键 词：瘙痒症 P物质 一氧化氮 一氧化氮合酶 动物实验 

分 类 号：R285.5[医药卫生—中药学]