Roscovitine对瑞芬太尼诱发大鼠切口痛的保护作用及机制分析  

Study on effect and mechanism of Roscovitine on remifentanil-induced hyperalgesia

作　　者：刘东亚[1] 李海英 韩快娟 崔艳田 LIU Dong-ya;LI Hai-ying;HAN Kuai-juan(Department of Anesthesiology,Hanzhong People's Hospital,Hanzhong Shaanxi 723000,China;Department of Anesthesiology,Xi'an Gaoxin Hospital,Xi'an Shaanxi 710075,China)

机构地区：[1]汉中市人民医院麻醉科,陕西汉中723000 [2]西安高新医院麻醉科,陕西西安710075

出　　处：《临床和实验医学杂志》2020年第21期2241-2245,共5页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金面上项目(编号:81772411)。

摘　　要：目的探究Roscovitine对瑞芬太尼诱发大鼠切口痛的保护作用及机制。方法采用随机数字表法将50只大鼠平均分为对照组(C组,DMSO+正常大鼠+皮下泵注0.9%氯化钠溶液)、瑞芬太尼组(R组,DMSO+切口痛模型大鼠+皮下泵注0.9%氯化钠溶液)、切口痛组(I组,DMSO+切口痛模型大鼠+泵注瑞芬太尼)、Roscovitine组(ROS组,Roscovitine+切口痛模型大鼠+皮下泵注0.9%氯化钠溶液)、Roscovitine+瑞芬太尼组(ROS+R组,Roscovitine+切口痛模型大鼠+泵注瑞芬太尼)。分别于干预前(T0)、干预后2 h(T1)、干预后6 h(T2)、干预后24 h(T3)以及干预后48h(T4)时测定各组大鼠的机械性缩足阈值(PWMT)、热缩足潜伏期(PWTL);采用免疫印迹(Western blotting)法测定脊髓谷氨酸转运体-1(GLT-1)、兴奋性G蛋白(GS);采用免疫沉淀联合Western blotting法测定脊髓硝基化GLT-1(n GLT-1)和硝基化GS(n GS)的表达水平;采用Gene Tools图像分析软件测定n GLT-1、GLT-1、n GS、GS条带灰度值,计算n GLT-1/GLT-1和n GS/GS值。结果T0时,各组大鼠PWMT在22 g左右,组间比较差异无统计学意义(P>0.05);与C组比较,后4组PWTL和PWMT均显著降低(P<0.05);与I组比较,R组T1~T4时PWTL和PWMT均开始显著降低(P<0.05);T1~T4时,ROS+R组PWTL和PWMT均明显高于R组(P<0.05)。与C组比较,I组、R组脊髓GLT-1和GS表达水平降低,n GLT-1和n GS表达水平增高,n GLT-1/GLT-1值和n GS/GS值升高(P<0.05),而I组和R组相比差异无统计学意义(P>0.05);与I、R组相比,ROS组、ROS+R组脊髓GLT-1和GS表达水平升高,n GLT-1和n GS表达水平以及n GLT-1/GLT-1值和n GS/GS值降低(P<0.05)。结论Roscovitine能够显著缓解瑞芬太尼所致大鼠切口痛,缓解痛觉过敏以降低大鼠疼痛程度,可能与上调GLT-1、GS表达、并下调n GLT-1、n GS表达有关。Objective To explore the protective effect and mechanism of Roscovitine on remifentanil-induced incision pain in rats.Methods Fifty rats were divided into a control group(C group,DMSO+normal rats+0.9%sodium chloride solution),remifentanil group(R group,DMSO+incision pain model rats+NS),incision pain group(group I,DMSO+incision Pain model rats+remifentanil),Roscovitine(ROS group,Roscovitine+incision pain model rats+0.9%sodium chloride solution),Roscovitine+remifentanil group(ROS+R group,Roscovitine+incision pain model rats+remifentanil)by random number table method.The mechanical foot withdrawal threshold(PWMT)and heat shrinkage foot latency(PWTL)of each group of rats were determined before the intervention(T0),2 h(T1),6 h(T2),24 h(T3),and 48 h(T4).Spinal glutamate transporter-1(GLT-1)and excitatory G protein(GS)were measured by Western blotting.Spinal cord nitrosylation GLT-1(nGLT-1)and nitrosylation GS(nGS)expression levels were determined by immunoprecipitation combined with Western blotting.The gray values of nGLT-1,GLT-1,nGS,and GS bands were determined using Gene Tools image analysis software,and nGLT-1/GLT-1 and n GS/GS values were calculated.Results At T0,the PWMT of rats in each group was about 22 g,and there was no significant difference between the groups(P>0.05).Compared with group C,the PWTL and PWMT of the last four groups were significantly reduced(P<0.05).Compared with group I,PWTL and PWMT of group R began to decrease significantly from T1~T4(P<0.05);from T1~T4,PWTL and PWMT in ROS+R group were significantly higher than those in R group(P<0.05).Compared with group C,the expression levels of GLT-1 and GS in the spinal cord of group I and group R decreased,the expression levels of n GLT-1 and n GS increased,and the ratio of nGLT-1/GLT-1 and n GS/GS increased(P<0.05),The difference between the two groups was not statistically significant(P>0.05);Compared with the I and R groups,the expression levels of GLT-1 and GS in the spinal cord of the ROS group and ROS+R group were increased,the expression leve

关 键 词：大鼠 痛觉过敏 ROSCOVITINE 瑞芬太尼 作用机制 

分 类 号：R614[医药卫生—麻醉学]