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溶血磷脂酸受体亚型1在溶血磷脂酸所致小鼠瘙痒中的作用
戴丽丽,王琦,王琼,邹李晶,高坡,焦英甫,孙继虎*
0
(第二军医大学基础部生理学教研室, 上海 200433
共同第一作者
*通信作者)
摘要:
目的 探明介导疼痛的溶血磷脂酸(lysophosphatidic acid, LPA)受体亚型1(LPA1)与LPA致痒的关系。方法 应用荧光定量PCR对LPA1~LPA6受体mRNA水平进行定量,用免疫荧光染色观察小鼠背根神经节(dorsal root ganglia,DRG)神经元中LPA1受体及胃泌素释放肽(gastrin-releasing peptide,GRP)的共表达,用区分痛和痒的"面颊模型"观察面颊部皮内注射LPA1和LPA3受体拮抗剂Ki16425后再注射LPA在正常小鼠瘙痒发生中的作用。结果 LPA1受体mRNA在外周感觉神经元表达丰富;LPA1受体在代表痒神经元的GRP阳性神经元表达;正常小鼠皮内注射LPA诱发疼痛反应,抑制LPA1受体后疼痛反应明显降低(P<0.01),搔抓反应(P<0.05)明显增加。结论 LPA1受体参与了LPA的致痒效应。
关键词:  溶血磷脂酸  溶血磷脂酸受体1  疼痛  瘙痒症
DOI:10.16781/j.0258-879x.2016.04.0401
投稿时间:2015-12-24修订日期:2016-02-22
基金项目:国家自然科学基金面上项目(31271256).
Role of lysophosphatidic acid receptor 1 in lysophosphatidic acid-induced pruritus in mice
DAI Li-li,WANG Qi,WANG Qiong,ZOU Li-jing,GAO Po,JIAO Ying-fu,SUN Ji-hu*
(Department of Physiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China
Co-first authors
*Corresponding author)
Abstract:
Objective To explore the role of lysophosphatidic acid receptor 1(LPA1), which mediates neuropathic pain, in LPA-induced pruritus in mice. Methods We applied real-time PCR to examine the relative LPA1-LPA6 mRNA level, immuno-staining to observe the co-expression of LPA1 with the gastrin-releasing peptide (GRP) in the neurons of dorsal root ganglia (DRG) of mice. "Cheek model" was used to count the scratching after intradermal injection of LPA in mice treated with the LPA1 and LPA3 receptor antagonists Ki16425. Results LPA1 mRNA was found highly expressed in the peripheral sensory neurons; LPA1 co-existed with GRP in the small-or medium-neurons of DRG of mice; an intradermal injection of LPA in mouse cheek produced pain-like wiping, but the pain response was significantly decreased after inhibition of LPA1 receptor with Ki16425(P<0.01), and itch-like scratching behavior was significantly increased (P<0.05). Conclusion These results suggest that down-regulation of LPA1 might lead to scratching behavior in mice treated with LPA.
Key words:  lysophosphatidic acid  lysophosphatidic acid receptor 1  pain  pruritus