氯胺酮对疼痛抑郁共病大鼠行为学及吲哚胺2,3二加氧酶信号通路的影响

目的观察氯胺酮对疼痛抑郁共病大鼠行为学及吲哚胺2,3二加氧酶(IDO)信号通路的影响。方法健康成年雄性SD大鼠24只,2月龄,体重200~250g,随机分为三组:对照组(S组)、生理盐水组(N组)和氯胺酮组(K组),每组8只。N组及K组大鼠均接受右踝关节腔内完全弗氏佐剂(CFA)50μl注射,建立疼痛抑郁共病模型;S组大鼠则注射生理盐水50μl作为对照。CFA注射后1、7、14d分别测定机械性缩足反射阈值(MWT)及不动时间。第14天行为学测试后,N组大鼠腹腔注射生理盐水1ml,K组则注射20 mg/kg氯胺酮1 ml。三组大鼠于腹腔注射后1h测定MWT及不动时间。随后取大鼠海马、前额皮层、扣带回组织及血浆,采用ELISA法测定IL-6浓度及IDO活性。结果与S组比较,N组及K组CFA注射后1、7、14dMWT明显降低(P0.05),CFA注射后7、14d不动时间明显延长(P0.05)。与N组比较,K组MWT明显升高(P0.05),不动时间明显缩短(P0.05),大鼠海马、前额皮层、扣带回IL-6浓度和IDO活性均明显下降(P0.05)。结论氯胺酮可有效治疗疼痛抑郁共病,这可能与其抑制大鼠不同脑区IDO信号通路活性有关。

Effects of ketamine on the behavior and indoleamine 2,3-dioxygenase signaling pathway in rats with pain and depression comorbidity

Objective To observe the effects of ketamine on the behavior and indoleamine 2,3-dioxygenase (IDO ) signaling pathway in the rats with pain and depression comorbidity. Methods Twenty-four male adult SD rats,aged 2 months,weighing 200-250 g,were randomized into three groups:control group (group S),saline group (group N)and ketamine group (group K), eight in each group.CFA (50 μl)was injected into the right tibiotarsal joint cavity to establish the model of pain and depression comorbidity in the groups N and K,whereas saline (50 μl)was injected in the group S.The mechanical withdrawal threshold (MWT)and the immobility time were measured 1,7,and 14 days after the CFA injection.After the behavioral tests 14 days after the CFA injection, saline (1 ml)was intraperitoneal administrated in the group N and ketamine 20 mg/kg (1 ml)was in-traperitoneal administrated in the group K 14 days after CFA injection.The MWT and immobility time were measured 1 h after administration in the three groups to evaluate the behavioral changes. Then,the hippocampus,prefrontal cortex,cingulated gyrus and plasma were harvested to determine the levels of IL-6 and IDO using an enzyme-linked immunosorbent assay after the behavioral tests. Results Compared with the group S,the MWT was decreased and the immobility time was signifi-cantly increased in the group N and group K (P <0.05).Compared with the group N,the MWT was increased (P <0.05),the immobility time was decreased (P <0.05),and the levels of IL-6 and IDO in the hippocampus,prefrontal cortex and cingulated gyrus were significantly decreased in the group K (P < 0.05 ).Conclusion Ketamine can effectively treat pain and depression comorbidity,which may be attributed to the inhibition of IDO signaling pathway in different brain regions of rats.