摘要
目的探讨IL-10经皮鞘内注射入福尔马林致痛小鼠蛛网膜下腔,观察其对小鼠的镇痛作用。方法选择成年雄性C57/B6小鼠21只,体重18~22 g,将其随机分为3组,空白对照组(C组)、假给药组(N组)和IL-10组(I组)。C组小鼠右侧后爪趾底注射生理盐水50μL,N组和I组小鼠经皮鞘内分别注射10μLPBS和IL-10,10 min后于右侧后爪趾底注射福尔马林50μL,给药后观察小鼠不同时间点的痛行为学变化。结果该实验致痛模型造模成功。N、I组与C组相比,每一时间点舔/咬时间延长,差异有统计学意义(P<0.05),机械性缩足阈值降低,差异有统计学意义(P<0.05);I组与N组相比,在5、10和30 min小鼠舔/咬时间缩短(P<0.05),机械性缩足阈值在5、15、20、25、30、35 min时升高,差异有统计学意义(P<0.05);给药后30 min测热甩尾阈值,N、I组比C组缩短,I组比N组明显延长,差异有统计学意义(P<0.05)。结论鞘内注射IL-10可明显缓解福尔马林致痛小鼠的痛行为反应。
Objective To investigate the analgesic effect of IL-10 on the subarachnoid space of formalin-induced pain mice by intrathecal injection of IL-10. Methods Twenty-one male C57/B6 mice were selected and weighed 18-22 g.They were randomly divided into three groups: blank control group(group C), sham group(group N) and IL-10 group(group I). Group C mice were injected with 50 μL of normal saline to the right hind paw. The mice in group N and group I were injected with 10 μL of PBS and IL-10 respectively. After 10 minutes, 50 μL of formalin was injected into the right hind paw. Pain behavioral changes at different time points in mice were observed after administration. Results The experimental pain model was successfully established. Compared with group C, the sputum/bite time was prolonged,the difference was statistically significant(P<0.05) and the mechanical contraction threshold was decreased,the difference was statistically significant(P<0.05). Group I was compared with group N at 5, 10 and 30 min licking/biting time of mice was shortened,the difference was statistically significant(P<0.05), the mechanical shrinkage threshold was increased at 5, 15, 20, 25, 30, 35 min,the difference was statistically significant(P<0.05); the thermal tail threshold was measured 30 min after administration, group N and I were shorter than group C, and group I was significantly longer than group N,the difference was statistically significant(P<0.05). Conclusion Intrathecal injection of IL-10 can significantly alleviate the pain behavioral response in formalin-induced pain mice.
引文
[1]苏漫,朱清,李俊旭.镇痛药物作用靶点的研究现状[J]中国药理学通报,2018;34(2):161-165.
[2]Cianciulli A,Dragone T,Calvello R,et al.IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells[J].Int Immun0pharmacol,2015,24(2):369-376.
[3]王素丽,陈莉媚,金彤,等.细风轮菜两种提取物的镇痛抗炎作用及其机制研究[J].中药药理与临床,2018,34(3):93-97.
[4]Boillee S,Yamanaka K,Lobsiger CS,et al.Onset and progression in inherited ALS determined by motor neurons and microglia[J].Science,2006(312):1389-1392.
[5]于布为,赵欣.疼痛机制研究进展[J].上海医学,2007,30(6):462-465.
[6]Park SH,Lee JR,Jang SP,et al.Antinociceptive profiles and mechanisms of centrally administered oxyntomodulin in various mouse pain models Antinociceptive profiles and mechanisms of centrally administered oxyntomodulin in various mouse pain models[J].Neuropeptides,2018(68):7-14.
[7]Zhang C,Ward J,Dauch JR,et al.Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome[J].PLoS One,2018;13(2)e0192333.
[8]兰岭,申乐,黄宇光.术后慢性疼痛相关炎症反应及炎症细胞因子研究进展[J].中国医学科学院学报,2015,37(6):741-745.
[9]赵慧慧,韩伟.盐酸羟考酮超前镇痛对福尔马林致痛模型大鼠疼痛行为和大鼠血液NO及P物质浓度的影响[J].中国兽医学报,2015,35(2):310-313.