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

Role of lysophosphatidic acid receptor 1 in lysophosphatidic acid-induced pruritus in mice

目的探明介导疼痛的溶血磷脂酸（lysophosphatidic acid,LPA）受体亚型1（LPA_1）与LPA致痒的关系。方法应用荧光定量PCR对LPA_1～LPA_6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LPA_1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LPA_1和LPA_3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 LPA_1受体mRNA在外周感觉神经元表达丰富;LPA_1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LPA_1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 LPA_1受体参与了LPA的致痒效应。

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, 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.