脊髓P2Y1R在瑞芬太尼诱发切口痛大鼠痛觉过敏形成中的作用:与脊髓NR1和NR2B功能的关系  

Role of spinal P2Y1R in development of remifentanil-induced hyperalgesia in rats with incisional pain:relationship with function of NR1 and NR2B in spinal cord

作　　者：苏林[1] 白晓清 赵亓[1] 郭素倩 王国林[1] 于泳浩[1] Su Lin;Bai Xiaoqing;Zhao Qi;Guo Suqian;Wang Guolin;Yu Yonghao(Department of Anesthesiology,Tianjin Medical University General Hospital Tianjin Research Institute of Anesthesiology,Tianjin 300052,China;Department of Science and Education,Tianjin Beichen Hospital,Tianjin 300400,China)

机构地区：[1]天津医科大学总医院麻醉科,天津市麻醉学研究所,300052 [2]天津市北辰医院科教科,300400

出　　处：《中华麻醉学杂志》2021年第8期978-983,共6页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81500961);天津市北辰区科技计划项目(2018-SHGY-07)。

摘　　要：目的评价脊髓P2Y1嘌呤受体(P2Y1R)在瑞芬太尼诱发切口痛大鼠痛觉过敏形成中的作用及其与脊髓NMDA受体(NR)1和NR2B功能的关系。方法鞘内置管成功的健康成年雄性SD大鼠48只,10~12周龄,体重250~280 g,采用随机数字表法分为6组(n=8):对照组(C组)、P2Y1R拮抗剂MRS2179组(M组)、瑞芬太尼组(R组)、瑞芬太尼+MRS2179组(R+M组)、切口痛+瑞芬太尼组(I+R组)和切口痛+瑞芬太尼+MRS2179组(I+R+M组)。C组鞘内注射生理盐水10μl,10 min后经尾静脉输注生理盐水0.1 ml·kg^(-1)·min^(-1) 60 min;M组鞘内注射MRS21790.6 nmol/kg,10 min后经尾静脉输注生理盐水0.1 ml·kg^(-1)·min^(-1) 60 min;R组鞘内注射生理盐水10μl,10 min后经尾静脉输注瑞芬太尼1μg·kg^(-1)·min^(-1) 60 min;R+M组鞘内注射MRS21790.6 nmol/kg,10 min后经尾静脉输注瑞芬太尼1μg·kg^(-1)·min^(-1) 60 min;I+R组鞘内注射生理盐水10μl,10 min后经尾静脉输注瑞芬太尼1μg·kg^(-1)·min^(-1) 60 min,瑞芬太尼输注开始后10 min制备切口痛模型;I+R+M组鞘内注射MRS21790.6 nmol/kg,10 min后经尾静脉输注瑞芬太尼1μg·kg^(-1)·min^(-1) 60 min,瑞芬太尼输注开始后10 min制备切口痛模型。分别于输注瑞芬太尼或生理盐水前24 h、输注停止后2、6、24和48 h时测定机械缩足反应阈(MWT)、热缩足潜伏期(TWL)和冷板抬足次数。最后一次痛阈测定结束后处死大鼠,取脊髓L4-6节段,采用Western blot法检测脊髓P2Y1R、磷酸化NR1(p-NR1)、NR1、磷酸化NR2B(p-NR2B)和NR2B表达,并计算p-NR1/NR1比值及p-NR2B/NR2B比值,采用RT-PCR法检测P2Y1R、NR1和NR2B的mRNA表达。结果与C组比较,R组MWT降低,TWL缩短,冷板抬足次数增加,脊髓P2Y1R及其mRNA、NR1及其mRNA、p-NR1、NR2B及其mRNA、p-NR2B表达上调,p-NR1/NR1比值和p-NR2B/NR2B比值升高(P<0.01)。与R组比较,R+M组MWT增加,TWL延长,冷板抬足次数减少,脊髓P2Y1R、p-NR1、NR1及其mRNA、p-NR2B、NR2B及其mRNA表达下调,p-NR1/NR1比值和p-NR2B/NR2B比�Objective To evaluate the role of spinal P2Y1R in the development of remifentanil-induced hyperalgesia in rats with incisional pain(IP)and the relationship with the function of NR1 and NR2B in spinal cord.Methods Forty-eight healthy adult male Sprague-Dawley rats,aged 10-12 weeks,weighing 250-280 g,in which intrathecal catheters were successfully placed,were divided into 6 groups(n=8 each)using a random number table method:control group(group C),P2Y1R antagonist MRS2179 group(group M),remifentanil group(group R),remifentanil plus MRS2179 group(group R+M),IP plus remifentanil group(group I+R)and IP plus remifentanil plus MRS2179 group(group I+R+M).In group C,normal saline 10μl was intrathecally injected,and 10 min later normal saline was infused for 60 min via the tail vein at a rate of 0.1 ml·kg^(-1)·min-1.In group M,MRS21790.6 nmol/kg was intrathecally injected,and 10 min later normal saline was infused for 60 min via the tail vein at a rate of 0.1 ml·kg^(-1)·min^(-1).In group R,normal saline 10μl was intrathecally injected,and 10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1μg·kg^(-1)·min^(-1).In group R+M,MRS21790.6 nmol/kg was intrathecally injected,and 10 min later remifentanil was infused for 60 min at a rate of 1μg·kg^(-1)·min^(-1) via the tail vein.In group I+R,normal saline 10μl was intrathecally injected,10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1μg·kg^(-1)·min^(-1),and IP was established at 10 min after onset of remifentanil infusion.In group I+R+M,MRS21790.6 nmol/kg was intrathecally injected,10 min later remifentanil was infused via the tail vein for 60 min at a rate of 1μg·kg^(-1)·min^(-1),and IP was established at 10 min after onset of remifentanil infusion.The mechanical paw withdrawal threshold(MWT),thermal paw withdrawal latency(TWL),and the number of paw lifts on the cold plate were measured at 24 h before infusion of remifentanil or normal saline and at 2,6,24,and 48 h after the end of infusion.The animal

关 键 词：哌啶类 痛觉过敏 受体 嘌呤能P2Y1 受体 N-甲基-D-天冬氨酸 脊髓 

分 类 号：R614[医药卫生—麻醉学]