IL-6/IDO信号通路在氯胺酮治疗大鼠疼痛抑郁共病模型中的作用  

Role of IL-6/IDO pathway in therapeutic effects of ketamine on comorbidity of pain and depression in rats

作　　者：郭杰[1] 王菁[2] 谢泽敏[2] 唐小慧[2] 张广芬[2] 郑曼[1] 沈锦春[2] 

机构地区：[1]江苏省中医院麻醉科,210029 [2]南京大学医学院临床学院(南京军区南京总医院)麻醉科

出　　处：《江苏医药》2016年第14期1536-1539,共4页Jiangsu Medical Journal

基　　金：国家自然科学基金(81503053;81571083)

摘　　要：目的观察IL-6/吲哚胺2,3-二加氧酶(IDO)信号通路在氯胺酮治疗大鼠疼痛抑郁共病模型中的作用。方法第一部分:32只SD雄性大鼠随机均分为四组:生理盐水1、24h组(S1组、S24组)和氯胺酮1、24h组(K1组、K24组)。所有大鼠右踝关节腔内注射完全弗氏佐剂(CFA)50μl建立疼痛抑郁共病模型。CFA注射后第14天,按照分组腹腔注射生理盐水和氯胺酮,给药后1、24h测定机械性缩足反射阈值(MWT)和强迫游泳实验不动时间。行为学测试后,取海马检测IL-6和IDO水平。第二部分:32只SD雄性大鼠随机均分为四组:PBS+生理盐水组(PS组)、PBS+氯胺酮组(PK组)、IL-6+生理盐水组(IS组)和IL-6+氯胺酮组(IK组)。大鼠行海马区置管,同时建立疼痛抑郁共病模型。CFA注射后第7天开始,按照分组分别海马区给予PBS 0.5μl或IL-6 0.1μg,连续7d。CFA注射后第14天,按照分组腹腔注射生理盐水或氯胺酮,给药后1h测定MWT和强迫游泳实验不动时间。行为学测试后,取海马检测IL-6水平。结果第一部分:与S1组相比,K1组大鼠MWT增加,强迫游泳不动时间、海马IL-6和IDO水平均下降(P<0.05);与S24组相比,K24组大鼠MWT增加,不动时间、IL-6和IDO水平均下降(P<0.05)。第二部分:与PS组相比,PK组MWT增加,不动时间和IL-6水平下降(P<0.05),IS组MWT下降,不动时间和IL-6水平增加(P<0.05)。与IS组相比,IK组MWT和不动时间均无统计学差异(P>0.05),但IL-6水平下降(P<0.05)。与PK组相比,IK组MWT下降,不动时间和IL-6水平增加(P<0.05)。结论氯胺酮可通过抑制海马IL-6/IDO信号通路对疼痛抑郁共病大鼠产生治疗作用。Objective To investigate the role of interleukin-6（IL-6）/indoleamine 2,3-dioxygenase（IDO）pathway in the therapeutic effects of ketamine on the comorbidity of pain and depression in rats.Methods Part one：CFA 50μl was injected into the right tibiotarsal joint cavity for the establishment of the model of pain and depression comorbidity in 32 SD rats,which were equally randomized into 4groups of K1（measured at one hour after treated with ketamine）,K24（measured at24 hours after treated with ketamine）,S1（measured at one hour after treated with saline）and S24（measured at 24 hours after treated with saline）.The saline or ketamine was intraperitoneally administrated in the 14^（th） day after CFA injection.The mechanical withdrawal threshold（MWT）and immobility time of forced swimming test（FST）were measured at one hour or 24 hours after drug treatment to evaluate the changes of behavior in rats.The levels of IL-6and IDO in the hippocampus were measured after behavior tests.Part two：CFA 50μl was injected into the right tibiotarsal joint cavity for the establishment of the model of pain and depression comorbidity in 32 SD rats,which were equally randomized into 4groups of PS（treated with PBS＋saline）,PK（treated with PBS＋ketamine）,IS（treated with IL-6＋saline）and IK（treated with IL-6＋ketamine）.All rats were implanted with guide cannula into the hippocampus and the PBS 0.5μl or IL-6 0.1μg was injected daily into the hippocampus from the 7^（th） to 13^（th） day after CFA injection.Saline（in groups of PS and IS）or ketamine（in groups of PK and IK）was intraperitoneally administrated on the 14^（th） day after CFA injection.The MWT and immobility time of FST were measured at one hour after drug treatment to evaluate the changes of behavior in rats.Hippocampal IL-6level was measured after behavior tests.Results Part one：Compared with group S1,MWT was increased,and the immobility time and the levels of IL-6and IDO were decreased in group K1（P0.05）.C

关 键 词：白细胞介素6/吲哚胺2 3-二加氧酶信号通路 氯胺酮 疼痛 抑郁 

分 类 号：R687[医药卫生—骨科学]