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

发布时间：2018-03-08 04:12

本文选题：慢性炎性痛　切入点：瞬时受体电位通道　出处：《安徽医科大学学报》2017年12期 　论文类型：期刊论文

【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(P0.001),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(P0.001);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(P0.001);TRPM2~(-/-)CFA组足爪肿胀度明显低于WT CFA组(P0.001),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。
[Abstract]:Objective to investigate the effect of intrathecal injection of acyl aniline hydroxamic acid (SAHAA) on chronic inflammatory pain in mice mediated by M-type transient receptor potential channel (2TRPM2). According to the principle of randomized control, 8 groups were divided into 8 groups: CON group, WT DMSO group, WT CFA group, WT CFA group, SAHA group, WT SAHA group, TRPM2P -P -P) control group, TRPM2 / P% -CON group, TRPM2P / P / R group, TRPM2P / P / T group, TRPM2P / P / P group), the inflammatory group in the inflammatory group TRPM2- / -r / r / r / r / r, the inflammatory group in the inflammatory group TRPM2P / r / r / r / r / r / r / -C / P / P / P / -CON, respectively, in the control group and in the TRPM2 / r / r / r / r / r / r group of inflammatory pain SAHA group in the inflammatory group / / r / r / r / r / r / r ~ (-1) inflammatory SAHA group. The chronic inflammatory pain models were established by subcutaneous injection of 40 渭 l Freund's adjuvant CFAA 40 渭 l in the left hind limb of mice. The chronic inflammatory pain models were established in the SAHA group. The rats in the SAHA group were injected intrathecal with 50 mg/kg SAHAWT CON group, 50 mg/kg after behavioral test on the 9th day after the model was established. In the same dose of normal saline. WT and TRPM2 +-/ -%-DMSO group, intrathecal injection and SAHA of the same volume were used to measure the nociceptive threshold of mechanical stimulation in mice. The nociceptive threshold and the swelling degree of the feet were stimulated by radiation heat. Results TRPM2 +-/ -) mice showed a normal behavioral response to pain before modeling. There was no significant difference between WT mice and WT mice. WT and TRPM2T-1 / -) mice were injected intrathecally with DMSO.There was no significant difference in pain behavioral indexes between WT and WT mice before injection. The threshold of mechanical stimulation and thermal stimulation in WT CFA group was significant. Compared with WT CON group, P0.001 and WT SAHA group were treated with SAHA. Compared with WT CFA group, the pain threshold was significantly higher than that in WT CFA group. There was no significant difference between WT CFA group and TRPM2~(-/-)SAHA group. The degree of paw swelling in WT CFA group was significantly higher than that in TRPM2~(-/-)SAHA group. There was significant difference between WT CON group and WT SAHA group. The degree of paw swelling in TPM _ 2 / / -r ~ -C ~ (-1) CON group was significantly lower than that in WT CFA group (P 0.001), but there was no significant difference compared with TRPM2~(-/-)SAHA group. Conclusion TRPM2 is involved in the occurrence and development of chronic inflammatory pain in mice. Intrathecal injection of SAHA may improve chronic inflammatory pain mediated by TRPM2.
【作者单位】：安徽医科大学第一附属医院麻醉科;六安市人民医院麻醉科;
【基金】：国家自然科学基金青年基金(编号:81500949)
【分类号】：R614

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