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鞘内注射SAHA对M型瞬时受体电位通道2介导小鼠慢性炎性痛的影响

Effect of intrathecal injection of SAHA on chronic inflammatory pain in mice mediated by transient receptor potential melastatin 2
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摘要 目的探讨鞘内注射辛二酰苯胺异羟肟酸(SAHA)对M型瞬时受体电位通道2(TRPM2)介导小鼠慢性炎性痛的影响。方法将雄性野生型(WT)小鼠和TRPM2^(-/-)小鼠各32只,按随机对照原则分为8组:WT对照组(WT CON组)、WT溶媒组(WT DMSO组)、WT炎性痛组(WT CFA组)、WT炎性痛+SAHA组(WT SAHA组)、TRPM2^(-/-)对照组(TRPM2^(-/-)CON组)、TRPM2^(-/-)溶媒组(TRPM2^(-/-)DMSO组)、TRPM2^(-/-)炎性痛组(TRPM2^(-/-)CFA组)、TRPM2^(-/-)炎性痛+SAHA组(TRPM2^(-/-)SAHA组),每组8只。采用完全弗氏佐剂(CFA)40μl于小鼠左后肢足底皮下注射建立慢性炎性痛模型,WT和TRPM2^(-/-)的SAHA组于造模后3~9 d行为学测试后鞘内注射50 mg/kg的SAHA,WT CON组、WT CFA组、TRPM2^(-/-)CON组、TRPM2^(-/-)CFA组4组注射等量生理盐水。WT和TRPM2^(-/-)的DMSO组鞘内注射与SAHA等体积的DMSO。分别测定小鼠的机械刺激伤害感受阈、辐射热刺激伤害感受阈及足爪的肿胀度。结果TRPM2^(-/-)小鼠在未造模前表现出正常的疼痛行为学反应,与WT小鼠差异无统计学意义。WT和TRPM2^(-/-)小鼠鞘内注射DMSO,其疼痛行为学指标与未注射前差异无统计学意义。WT CFA组的机械刺激伤害感受阈值和热刺激伤害感受阈值均明显低于WT CON组(P<0.001),WT SAHA组在给予SAHA干预后,各种疼痛阈值显著升高,与WT CFA组比较差异有统计学意义(P<0.001);TRPM2^(-/-)CFA组机械刺激伤害感受阈值和辐射热刺激伤害感受阈值均明显高于WT CFA组,与TRPM2^(-/-)SAHA组比较差异无统计学意义。WT CFA组足爪肿胀度造模后明显升高,与WT CON组、WT SAHA组比较均差异有统计学意义(P<0.001);TRPM2^(-/-)CFA组足爪肿胀度明显低于WT CFA组(P<0.001),与TRPM2^(-/-)SAHA比较差异无统计学意义。结论 TRPM2参与小鼠慢性炎性痛的发生发展,鞘内注射SAHA可能改善TRPM2介导的慢性炎性痛。 Objective To explore the effect of intrathecal injection of suberoylanilide hydroxamic acid( SAHA) on chronic inflammatory pain in mice mediated by transient receptor potential melastatin 2( TRPM2). Methods 32 specific pathogen free( SPF) male wild type( WT) mice and 32 TRPM2^(-/-)male mice were randomly divided into8 groups: WT control group( WT CON),WT solvent group( WT DMSO),WT inflammatory pain group( WT CFA),WT inflammatory pain + SAHA group( WT SAHA),TRPM2^(-/-)control group( TRPM2^(-/-)CON),TRPM2^(-/-)solvent group( TRPM2^(-/-)DMSO),TRPM2^(-/-)inflammatory pain group( TRPM2^(-/-)CFA),and TRPM2^(-/-)inflammatory pain + SAHA group( TRPM2^(-/-)SAHA)( n = 8 each). Inflammatory pain model was induced by intraplantar injection with 40 μl of complete Freund's adjuvant( CFA) into the plantar surface of the left hind paw. WT SAHA group and TRPM2^(-/-)SAHA group received intrathecal injection of SAHA 50 mg/kg each morning after nociceptive testing. The mice received the same volume saline treatment in the WT CON group,WT CFA group,TRPM2^(-/-)CON group and TRPM2^(-/-)CFA group. The WT DMSO group and TRPM2^(-/-)DMSO group received intrathecal injection of the same volume DMSO treatment with SAHA group. The 50% paw withdrawal threshold,the paw withdrawal thermal latency and paw edema were measured after injection of CFA,respectively. Results The TRPM2^(-/-)mice showed normal sensitivity to mechanical and thermal stimuli compared with WT mice. After receiving intrathecal injection DMSO in WT and TRPM2^(-/-)mice,the changes of behavior had no significant difference compared with CON group. In WT mice,the 50% paw withdrawal threshold and paw withdrawal thermal latency in WT CFA was attenuated compared with that in WT CON,WT SAHA group( P〈0. 001);The paw edema of WT CFA group was significantly higher than that in WT CON,WT SAHA group( P〈0. 001). In TRPM2^(-/-)mice,the 50% paw withdrawal threshold and paw withdrawal thermal latency were significantly higher than that in WT CFA group( P〈0. 001),and there were no significant difference in the behavioral responses between TRPM2^(-/-)CFA and TRPM2^(-/-)SAHA group. The paw edema of inflammatory pain group was significantly lower than that in WT inflammatory pain group( P〈0. 001). Conclusion The chronic inflammatory pain development is mediated by TRPM2,and intrathecal injection of SAHA may improve the expression of TRPM2 in the chronic inflammatory pain.
出处 《安徽医科大学学报》 CAS 北大核心 2017年第12期1795-1799,共5页 Acta Universitatis Medicinalis Anhui
基金 国家自然科学基金青年基金(编号:81500949)
关键词 慢性炎性痛 瞬时受体电位通道2 辛二酰苯胺异羟肟酸 chronic inflammatory pain transient receptor potential melastatin 2 suberoylanilide hydroxamic acid
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