噻吩诺啡抑制阿片及非阿片类物质诱导的急性抓挠行为  

Thienorphine inhibited acute scratching behavior induced by opioids and non-opioids

作　　者：马芳 周培岚 苏瑞斌 MA Fang;ZHOU Pei-lan;SU Rui-bin(Nanjing University of Chinese Medicine,Nanjing 210046,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]南京中医药大学,江苏南京210046 [2]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《药学学报》2024年第4期965-971,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82273909).

摘　　要：本文旨在用急性阿片及非阿片类物质建立小鼠瘙痒模型,探究阿片受体部分激动剂噻吩诺啡对致痒物质所致急性瘙痒行为的影响,揭示噻吩诺啡改善急性瘙痒的作用机制。本文用无侵害性小鼠抓挠行为分析系统测试瘙痒行为。C57 BL/6J小鼠分别给予吗啡、蛙皮素(鞘内注射,i.t)或五羟色胺(5-hydroxytryptamine,5-HT)、氯喹(皮内注射,i.d),建立瘙痒模型,探究噻吩诺啡(0.75、1.5、3 mg·kg^(-1))对致痒物质所致急性瘙痒行为的作用和机制。采用Western blot检测噻吩诺啡对致痒物质诱导的小鼠脊髓段蛋白激酶Cδ(protein kinase Cδ,PKCδ)蛋白表达的影响。实验中所有操作均获得军事医学研究院实验动物伦理委员会批准(批准号:IACUC-2021-017W)。结果显示,吗啡(1 nmol)、蛙皮素(0.3 nmol)、5-HT(5 nmol)、氯喹(20 nmol)分别给药后皆能显著增加小鼠的抓挠行为。噻吩诺啡(1.5 mg·kg^(-1))能够显著抑制阿片类药物吗啡和非阿片类物质蛙皮素、5-HT、氯喹诱导的抓挠行为,并且噻吩诺啡能够明显逆转阿片类药物吗啡和非阿片类致痒物质5-HT诱导的PKCδ蛋白表达的变化。本研究表明,阿片受体部分激动剂噻吩诺啡具有广谱抗瘙痒作用,能够通过不同途径逆转PKCδ而抑制阿片类和非阿片物质诱导的瘙痒行为,为探究和治疗瘙痒提供了新的思路。The study established a mouse itch model induced by acute opioid and non-opioid pruritogens.The effects and mechanism of partial opioid agonist thienorphine on acute scratching behavior caused by opioid and non-opioid pruritogens was demonstrated.The noninvasive scratching behavior analysis system was established to test scratching behavior induced by morphine,bombesin,5-hydroxytryptamine(5-HT)or chloroquine in C57 BL/6J mice.The effect of thienorphine(0.75,1.5,3 mg·kg^(-1))on acute itch caused by above pruritogens were studied.The expression of protein kinase Cδ(PKCδ)in mouse spinal cord was detected by Western blot after pruritogens addition with or without thienorphine pretreatment.All operations in the experiment were approved by the Institutional Animal Care and Use Committee of the Academy of Military Medical Sciences(IACUC-2021-017W).The scratching behavior increased significantly under morphine(1 nmol,i.t),bombesin(0.3 nmol,i.t),5-HT(5 nmol,i.d)or chloroquine(20 nmol,i.d)treatment,respectively.Thienorphine(1.5 mg·kg^(-1))significantly inhibited the scratching behavior induced by the morphine,bombesin,5-HT and chloroquine.Thienorphine significantly reversed the changes in PKCδprotein expression induced by morphine or 5-HT.In conclusion,the partial opioid agonist thienorphine could inhibit scratching behavior induced by opioid and non-opioid pruritogens.It might reverse PKCδthrough different pathways to inhibit opioids and non-opioids induced scratching behavior,which provided a new idea for exploring and treating itch.

关 键 词：噻吩诺啡 瘙痒 阿片类 非阿片类 蛋白激酶C δ 瘙痒治疗 

分 类 号：R966[医药卫生—药理学]