鞘內(nèi)注射SAHA對M型瞬時(shí)受體電位通道2介導(dǎo)小鼠慢性炎性痛的影響
發(fā)布時(shí)間:2018-03-08 04:12
本文選題:慢性炎性痛 切入點(diǎn):瞬時(shí)受體電位通道 出處:《安徽醫(yī)科大學(xué)學(xué)報(bào)》2017年12期 論文類型:期刊論文
【摘要】:目的探討鞘內(nèi)注射辛二酰苯胺異羥肟酸(SAHA)對M型瞬時(shí)受體電位通道2(TRPM2)介導(dǎo)小鼠慢性炎性痛的影響。方法將雄性野生型(WT)小鼠和TRPM2~(-/-)小鼠各32只,按隨機(jī)對照原則分為8組:WT對照組(WT CON組)、WT溶媒組(WT DMSO組)、WT炎性痛組(WT CFA組)、WT炎性痛+SAHA組(WT SAHA組)、TRPM2~(-/-)對照組(TRPM2~(-/-)CON組)、TRPM2~(-/-)溶媒組(TRPM2~(-/-)DMSO組)、TRPM2~(-/-)炎性痛組(TRPM2~(-/-)CFA組)、TRPM2~(-/-)炎性痛+SAHA組(TRPM2~(-/-)SAHA組),每組8只。采用完全弗氏佐劑(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組于造模后3~9 d行為學(xué)測試后鞘內(nèi)注射50 mg/kg的SAHA,WT CON組、WT CFA組、TRPM2~(-/-)CON組、TRPM2~(-/-)CFA組4組注射等量生理鹽水。WT和TRPM2~(-/-)的DMSO組鞘內(nèi)注射與SAHA等體積的DMSO。分別測定小鼠的機(jī)械刺激傷害感受閾、輻射熱刺激傷害感受閾及足爪的腫脹度。結(jié)果TRPM2~(-/-)小鼠在未造模前表現(xiàn)出正常的疼痛行為學(xué)反應(yīng),與WT小鼠差異無統(tǒng)計(jì)學(xué)意義。WT和TRPM2~(-/-)小鼠鞘內(nèi)注射DMSO,其疼痛行為學(xué)指標(biāo)與未注射前差異無統(tǒng)計(jì)學(xué)意義。WT CFA組的機(jī)械刺激傷害感受閾值和熱刺激傷害感受閾值均明顯低于WT CON組(P0.001),WT SAHA組在給予SAHA干預(yù)后,各種疼痛閾值顯著升高,與WT CFA組比較差異有統(tǒng)計(jì)學(xué)意義(P0.001);TRPM2~(-/-)CFA組機(jī)械刺激傷害感受閾值和輻射熱刺激傷害感受閾值均明顯高于WT CFA組,與TRPM2~(-/-)SAHA組比較差異無統(tǒng)計(jì)學(xué)意義。WT CFA組足爪腫脹度造模后明顯升高,與WT CON組、WT SAHA組比較均差異有統(tǒng)計(jì)學(xué)意義(P0.001);TRPM2~(-/-)CFA組足爪腫脹度明顯低于WT CFA組(P0.001),與TRPM2~(-/-)SAHA比較差異無統(tǒng)計(jì)學(xué)意義。結(jié)論 TRPM2參與小鼠慢性炎性痛的發(fā)生發(fā)展,鞘內(nèi)注射SAHA可能改善TRPM2介導(dǎo)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.
【作者單位】: 安徽醫(yī)科大學(xué)第一附屬醫(yī)院麻醉科;六安市人民醫(yī)院麻醉科;
【基金】:國家自然科學(xué)基金青年基金(編號:81500949)
【分類號】:R614
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