氯胺酮联合电休克对抑郁样大鼠海马炎症及β淀粉样蛋白的影响

Effects of ketamine combined with electroconvulsive shock on inflammation and amyloid-beta peptide in hippocampus of depressive rats

目的探讨氯胺酮联合电休克对抑郁样大鼠海马炎症及可溶性β淀粉样蛋白的影响。方法选取成年雄性SD大鼠48只,采用慢性不可预见性轻度应激建立大鼠抑郁模型。建模成功后将其随机分为4组,每组12只:抑郁组(D组)、电休克组(DE组)、氯胺酮联合电休克组(DKE组)和氯胺酮组(DK组)。D组大鼠行伪电休克处理;DE组大鼠行电休克处理;DKE组大鼠腹腔注射氯胺酮100 mg/kg后行电休克处理;DK组大鼠腹腔注射氯胺酮100 mg/kg后行伪电休克处理。Morris水迷宫评价大鼠学习记忆能力,荧光定量PCR和ELISA分别检测海马炎性细胞因子和可溶性Aβ浓度。结果电休克处理前,各组大鼠的逃避潜伏期、空间探索时间差异均无统计学意义(P>0.05);电休克处理后,与DE组相比,DKE组大鼠逃避潜伏期明显缩短、空间探索时间明显延长,海马IL-1β、TNF-αmRNA表达下调,Aβ1-40、Aβ1-42浓度降低,差异均具有统计学意义(P<0.05)。结论氯胺酮能够减轻抑郁大鼠电休克后学习记忆损伤,其机制与氯胺酮有效抑制电休克诱导的中枢炎症和降低海马β淀粉样蛋白水平有关。

Objective To investigate the effects of ketamine combined with electroconvulsive shock （ECS） on inflammation and amy- loid-beta peptide in hippocampus of depressive rats. Methods Chronic unpredictable mild stress （CUMS） was used to generate animal mod- els of depression. Forty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups （n ： 12） ：depression model group （group D）, electroconvulsive shock group （group DE）, ketamine combined with electroconvulsive shock group （group DKE）, and ketamine group （group DK）. Rats in group D received sham ECS treatment ;rats in group DE received ECS treatment;rats in group DKE were given intraper-itoneal injection of ketamine （100 mg/kg） and then received ECS treatment ;rats in group DK were given iatraperitoneal injection of ketamine （ 100 mg/kg） and then received sham ECS treatment. Morris water maze was used to assess the memory abilities of rats. The expression levels of IL-1β and TNF-α were measured by real-time PCR. Enzyme-linked immunosorbent assays were used to detect the levels of soluble Aβ. Results Before the administration of ECS or ketamine treatment,there was no significant difference in the escape latencies and space explo- ration time between the 4 groups （P 〉0.05 ）. After the ECS and ketamine treatment,rats of group DKE exhibited a shorter escape latencies and a longer space exploration time,and the expression of IL-1β and TNF-α mRNA were down-regulated while the concentration of Aβ1-40 and Aβ1-42 were increased compared with group DE with significant difference （P 〈 0.05 ）. Conclusion Ketamine can alleviate ECS-in- duced learning and memory impairments in depressive rats. This cognition-protecting effect of ketamine may be attributed to its suppression of ECS-induced neuroinflammation and decrease of the levels of soluble Aβ in the hippocampus of depressive rats.