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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 IL-6 / indoleamine 2,3-dioxygenase (IDO) signaling pathway in the ketamine-treated rat model of depression and pain. Methods The first part: 32 SD male rats were randomly divided into four groups: saline 1,24h group (S1 group, S24 group) and ketamine 1,24h group (K1 group, K24 group). All rats were injected intraperitoneally with 50μl Freund’s adjuvant (CFA) into the right ankle joint to establish a model of pain depression and co-morbidity. On the 14th day after CFA injection, saline and ketamine were injected intraperitoneally into the subgroups. The mechanical contracting threshold (MWT) and forced swimming experiment immobilization time were measured at 1 and 24 hours after administration. After behavioral testing, hippocampal IL-6 and IDO levels were measured. The second part: 32 SD male rats were randomly divided into four groups: PBS + saline group (PS group), PBS + ketamine group (PK group), IL-6 + saline group (IS group) and IL- Ketamine group (IK group). Rats were placed in the hippocampus area, while establishing a model of pain and depression. From the 7th day after CFA injection, 0.5μl of PBS or 0.1μg of IL-6 was given to the hippocampus separately for 7 days. On the 14th day after CFA injection, saline and ketamine were injected intraperitoneally according to the grouping, and the immobility time of MWT and forced swimming test was determined at 1 hour after administration. After behavioral testing, hippocampal IL-6 levels were taken. Results Compared with S1 group, the MWT of rats in K1 group increased, forced swimming time was fixed, the level of IL-6 and IDO in hippocampus decreased (P <0.05); Compared with S24 group, MWT in K24 group increased , Immobility time, IL-6 and IDO levels were decreased (P <0.05). The second part: Compared with the PS group, the MWT of PK group increased, the immobility time and IL-6 level decreased (P <0.05), the MWT of IS group decreased, the immobility time and IL-6 level increased (P <0.05). Compared with IS group, there was no significant difference in MWT and immobility time in IK group (P> 0.05), but IL-6 level decreased (P <0.05). Compared with PK group, IK group MWT decreased, immobility time and IL-6 levels increased (P <0.05). Conclusion Ketamine can inhibit the depression of the hippocampal IL-6 / IDO signaling pathway in the treatment of pain and depression in rats.