中国药理学通报2018，Vol.34Issue(4)：517-522,6.DOI:10.3969/j.issn.1001-1978.2018.04.016
下丘脑室旁核Epac蛋白在大鼠炎性痛调节过程中的作用及其机制研究
Role and mechanism of Epac protein in regulation of inflammatory pain in paraventricular nucleus of hypothalamus
摘要
Abstract
Aim To investigate the role and mecha-nism of exchange protein directly activated by cAMP (Epac) protein in the paraventricular nucleus(PVN) of the hypothalamus in the development of inflammatory pain in rats. Methods Adult SD male rats were cho-sen to establish the model of inflammatory pain through subcutaneous injection of complete Freund's adjuvant(CFA) on the center of left hind foot. Western blot was used to detect the changes of the expression of Ep-ac protein. Thermal withdrawal latency(TWL) was ob-served after the PVN injecting 8p-CPT-2′-O-Me-cAMP (8p-CPT),the agonist of Epac. Then activated down-stream MEK1/2 protein of Epac in PVN was detected using Western blot when the potency was the strongest.Results ① Compared with normal saline(control group),TWL decreased significantly on d 1, d 3, d 5, d 7,d 9 on the ipsilateral foot of CFA group rats(P<0.01),whereas it returned to normal level in d 13;the paw mechanical withdrawal threshold(PMWT) de-creased significantly on d 6,d 8,d 10,d 12 and d 14 (P<0.05);②Compared with the control,the Epac1 protein in CFA group rats began to decrease from d 3, and significantly decreased on d 3 and d 9(P<0.05), however the expression of Epac2 had no significant change, meanwhile p-MEK1/2 protein decreased sig-nificantly on d 3(P<0.05);③Compared with micro-injection of saline into the PVN(Saline group), the heat hyperalgesia of 20 min and 1h decreased signifi-cantly and TWL increased significantly after PVN ad-ministration of 8p-CPT(8p-CPT group)(P <0.05);paraventricular nucleus p-MEK1/2 protein expression increased significantly in 30 min(P <0.05) and re-covered to normal level 2 h after administration. Con-clusion The Epac1-MEK1/2 signaling pathway in the paraventricular nucleus of the hypothalamus may be in-volved in the development of chronic inflammatory pain induced by CFA.关键词
Epac/下丘脑室旁核/炎症性疼痛/p-MEK1/2/完全弗氏佐剂/8p-CPT-2′-O-Me-cAMPKey words
Epac/paraventricular nucleus of hypo-thalamus/inflammatory pain/p-MEK1/2/complete Freund′s adjuvant/8p-CPT -2′-O-Me-cAMP分类
医药卫生引用本文复制引用
陈彬彬,黄思婷,花景煜,杜雷,姬宁宁,宋昱,章功良,张咏梅..下丘脑室旁核Epac蛋白在大鼠炎性痛调节过程中的作用及其机制研究[J].中国药理学通报,2018,34(4):517-522,6.基金项目
国家自然科学基金资助项目(No 81771203,81772065) （No 81771203,81772065）
江苏省自然科学基金资助项目(No BK20161171) （No BK20161171）
