小肠过表达Ski蛋白对扭体小鼠的抑炎镇痛作用  

Anti-inflammatory and analgesic effects of small intestineSki-overexpression on acetic acid-induced writhing mice

作　　者：熊翱 魏小雨 彭艳 杨明 杨钱冬 罗飞 XIONG Ao;WEI Xiaoyu;PENG Yan;YANG Ming;YANG Qiandong;LUO Fei(Department of Orthopaedics,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing 400038,China;Research Institute of Surgery,Army Characteristic Medical Center of the Chinese People’s Liberation Army,Chongqing 400042,China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院骨科,重庆400038 [2]陆军军医大学陆军特色医学中心野战外科研究部,重庆400042

出　　处：《中国实验动物学报》2024年第3期369-377,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：重庆市研究生(博士)科研创新课题(CYB23292);陆军军医大学优秀人才库重点扶持对象(XZ-2019-505-021)。

摘　　要：目的 研究小肠过表达鸟类癌基因(virus sloan-kettering institute, v-ski)的细胞内同源物(Ski)蛋白对醋酸致扭体小鼠的抑炎镇痛作用。方法 选取8周龄雄性ICR小鼠,给予腹腔注射现配的0.7%醋酸溶液(0.1 mL/10 g)诱发扭体反应。实验小鼠分为假手术(sham)组、醋酸(acetic acid)组、醋酸(acetic acid)+布洛芬(ibuprofen)组、醋酸(acetic acid)+腺病毒空质粒(ad-EGFP)组、醋酸(acetic acid)+腺病毒ski质粒(ad-ski)-1组、醋酸(acetic acid)+腺病毒ski质粒(ad-ski)-2组和醋酸(acetic acid)+柳氮磺胺吡啶(sulfasalazine)组,每组10只。观察并记录第1次扭体出现的潜伏期,同时记录15 min内的扭体次数。获取标记的小肠组织,鉴定腺病毒转染效果,检测促炎因子、疼痛生物标志物的蛋白表达量,进一步分析核转录因子-κB(NF-κB)通路蛋白表达及其与Ski蛋白的结合情况。结果 腹腔注射ad-ski腺病毒后,小肠成功过表达Ski蛋白。过表达的Ski蛋白延长了小鼠发生扭体的潜伏期,同时减少了扭体反应的频率,与布洛芬的效果相当(P>0.05)。与醋酸组比较,过表达的Ski蛋白显著抑制了促炎因子和疼痛生物标志物的蛋白表达(P<0.05)。而且NF-κB p65与Ski有复合物形成。结论过表达Ski蛋白对醋酸引起的炎性疼痛有抑炎镇痛作用,且与Ski调节NF-κB信号通路有关。Objective To study the anti-inflammatory and analgesic effects of Ski protein overexpression on writing in mice induced by acetic acid.Methods Eight-week-old male ICR mice were administered 0.7%acetic acid solution(0.1 mL/10 g)to induce a writhing reaction.The mice were divided into sham,acetic acid,acetic acid+ibuprofen,acetic acid+ad-EGFP,acetic acid+ad-ski-1,acetic acid+ad-ski-2,and acetic acid+sulfasalazine groups(n=10 mice per group).The time to the first appearance of twisting and the number of twists within 15 min were recorded.Small intestine tissues were removed to identify the effect of adenovirus transfection and to detect protein expression levels of pro-inflammatory factors and pain biomarkers and protein expression of nuclear factor(NF)-κB p65 and its binding with Ski protein.Results Ski protein was successfully overexpressed in small intestine after intraperitoneal injection of Ad-ski adenovirus.Overexpressed Ski protein delayed the start and decreased the frequency of writhing,comparable to ibuprofen(P>0.05).Groups in which ski protein was overexpressed showed significantly inhibited protein expression of pro-inflammatory factors and pain biomarkers compared with the acetic acid group(P<0.05).Moreover,NF-κB p65 formed complexes with Ski.Conclusions Overexpression of Ski protein has anti-inflammatory and analgesic effects on acetic acid-induced inflammatory pain by inhibiting the expression of inflammatory factors and pain biomarkers,via regulation of the NF-κB signaling pathway.

关 键 词：SKI 扭体实验 白细胞介素-1Β 肿瘤坏死因子-α 神经生长因子 酪氨酸蛋白激酶A 小鼠 

分 类 号：Q95-33[生物学—动物学]