miR-146a对急性痛风性关节炎大鼠炎症反应的影响及其可能机制  

Effects of miR-146a on inflammatory response in rats with acute gouty arthritis and its possible mechanism

作　　者：樊丰夷[1] 蓝天座[1] 杨旸[1] 邓超[1] 张春 罗安电 FAN Feng-yi;LAN Tian-zuo;YANG Yang;DENG Chao;ZHANG Chun;LUO An-dian(Department of Nephrology,the First People's Hospital of Guiyang,Guiyang 550004,China)

机构地区：[1]贵州省贵阳市第一人民医院肾内科,贵阳市550004

出　　处：《广西医学》2022年第11期1260-1264,共5页Guangxi Medical Journal

基　　金：贵州省贵阳市科技计划(2019-9-8)。

摘　　要：目的探讨miR-146a对急性痛风性关节炎(GA)大鼠炎症反应的影响及其可能机制。方法将40只健康SD大鼠随机分为空白组、模型组、agomiR-146a组、antagomiR-146a组,每组10只。除空白组外,其余各组采用踝关节腔注射尿酸钠晶体的方法构建急性GA模型,于造模当天及造模后3 d、5 d、7 d、10 d,agomiR-146a组、antagomiR-146a组分别给予注射10μL agomiR-146a、10μL antagomiR-146a,空白组、模型组给予注射等量生理盐水。造模后10 d,观察4组大鼠踝关节滑膜组织的病理变化;采用ELISA检测4组大鼠滑膜组织中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1、IL-6的表达水平;采用实时荧光定量PCR法检测4组大鼠滑膜组织中NALP3、TNF-α、IL-1β的mRNA表达量;采用Western blot检测4组大鼠滑膜组织中NALP3、白细胞介素前体1β(pro-IL-1β)的蛋白表达量。结果模型组大鼠滑膜组织衬里下层有大量炎性细胞浸润,agomiR-146a组大鼠滑膜结构清晰完整,无炎性细胞浸润及纤维组织增生。与空白组相比,模型组滑膜组织TNF-α、IL-1、IL-6表达水平,NALP3、IL-1β、TNF-αmRNA表达水平,NALP3、pro-IL-1β蛋白表达水平均升高(均P<0.05);与模型组比较,agomiR-146a组滑膜组织中TNF-α、IL-1、IL-6表达水平,NALP3、IL-1β、TNF-αmRNA表达水平,NALP3、pro-IL-1β蛋白表达水平均降低(均P<0.05);与模型组相比,antagomiR-146a组滑膜组织中NALP3、IL-1β、TNF-αmRNA表达水平及NALP3、pro-IL-1β蛋白表达水平均无明显变化(均P>0.05),但滑膜组织中TNF-α、IL-1、IL-6表达水平升高(均P<0.05)。结论miR-146a高表达可降低急性GA模型大鼠踝关节滑膜组织的炎症因子水平,抑制踝关节滑膜组织NALP3的激活,其有望成为治疗急性GA的新靶点。Objective To investigate the effects of miR-146a on inflammatory response in rats with acute gouty arthritis(GA)and its possible mechanism.Methods Forty healthy SD rats were randomly assigned to blank group,model group,agomiR-146a group,or antagomiR-146a group,with 10 rats in each group.Except for the blank group,the acute GA model was established by injecting monosodium urate monohydrate into the ankle joint cavity in the remaining groups.On the day of modeling and three,five,seven and 10 days after modeling,the agomiR-146a group and the antagomiR-146a group were given injections of 10μL of agomiR-146a and 10μL of antagomiR-146a,respectively,whereas the blank and model groups were given injections of equivalent volume of normal saline.The pathological changes of rats'ankle joint synovial tissues in the four groups were observed 10 days after modeling;ELISA was employed to detect the expression levels of the indices with respect to tumor necrosis factorα(TNF-α),interleukin(IL)-1,and IL-6,in rats'synovial tissues in the four groups;real-time fluorescent quantitative PCR was used to detect the mRNA expression of NALP3,TNF-α,and IL-1β in rats'synovial tissues in the four groups;Western blot was employed to detect the protein expression of NALP3 and precursor interleukin 1β(pro-IL-1β)in rats'synovial tissues in the four groups.Results A large number of inflammatory cells showed infiltration in the sublining layer of rats'synovial tissues in the model group,and rats in the agomiR-146a group exhibited a distinct and intact synovial structure,without infiltration of inflammatory cells or hyperplasia of fibrosis tissues.Compared with the blank group,the model groups depicted elevated expression levels of TNF-α,IL-1,and IL-6,elevated mRNA expression levels of NALP3,IL-1β,and TNF-α,and elevated protein expression levels of NALP3 and pro-IL-1β in synovial tissues(all P<0.05);in comparison with the model group,the agomiR-146a group exhibited declines in TNF-α,IL-1,and IL-6 expression levels,declines in mRNA expr

关 键 词：急性痛风性关节炎 微小RNA-146a NALP3 炎症因子 大鼠 

分 类 号：R684.3[医药卫生—骨科学]