氯胺酮对疼痛抑郁共病大鼠海马ERK/CREB信号通路的影响

Effects of Ketamine on the Hippocampus ERK/CREB Signal Pathway in Rats with Pain and Depression Comorbidity

目的研究氯胺酮对疼痛抑郁共病大鼠海马ERK/CREB信号通路的影响。方法将38只大鼠随机分为对照组(n=10)和造模组(n=28),造模组采用牛Ⅱ型胶原-完全弗氏佐剂注射。采用机械缩足反应阈值测定(MWT)、强迫游泳实验(FST)判断造模成功后,将模型组随机平均分为氯胺酮组和生理盐水组。采用MWT、FST检测氯胺酮对疼痛抑郁共病的治疗作用。采用免疫印迹法检测大鼠海马组织中磷酸化的ERK1/2、CREB蛋白表达量。结果与生理盐水组比较,氯胺酮组大鼠的FST不动时间缩短,MWT阈值增加(P均<0.05)。氯胺酮组大鼠海马p ERK1/2、p CREB表达量均明显高于生理盐水组(P<0.05)。结论氯胺酮能够有效改善疼痛抑郁共病大鼠的疼痛及抑郁症状,其作用机制可能与海马ERK/CREB信号通路有关。

Objective To study the effect of ketamine on hippocampus ERK/CREB signal pathway in rats with pain and depression comorbidity. Methods 38 rats were randomly divided into control group （n = 10） and model group （n = 28）. The model group was injected bovine II collgen-complete Freund＇s adjuvant. After establishment of model of pain and depression comorbidity was verified by mechanical withdrawal threshold （MWT） and forced swimming test （FST）, the rats in model group were divided into ketamine group and saline group equally. The treatment effect of ketamine on pain and depression comorbidity was detected by MWT and FST. The expressions of phosphorylated ERK1/2 and CREB protein in hippocampus of rats were detected by Western blot. Results Compared with saline group, the FST motionless time of ketamine group decreased, and the MWT threshold increased （both P 〈0.05）. The expressions of hippocampus pERK1/2 and pCREB of ketamine group were significantly higher than those of control group （P 〈0.05）. Conclusions Ketamine can effectively improve the pain and depression symptom of rats with pain and depression comorbidity, whose mechanism of action may be related to the hippocampus ERK/CREB signal pathway.