摘要
目的观察右美托咪啶对坐骨神经慢性压迫性损伤(CCI)所致神经病理性疼痛大鼠的镇痛作用以及对脊髓p38丝裂原活化蛋白激酶(p38MAPK)和脑源性神经营养因子(BDNF)mRNA表达的影响。方法雄性SD大鼠72只,随机分为3组,每组24只,分别为假手术组(S组)、CCI组(C组)和右美托咪啶组(D组),S组大鼠仅分离坐骨神经不结扎,C组和D组建立CCI模型,D组于CCI术后即刻开始至取材时点每天腹腔注射右美托咪啶50μg/kg,S组和C组注射相同体积的生理盐水。各组大鼠分别于术前l d,术后1、3、7、14d测定机械痛阈和热痛阈,在术后第1、3、7、14d测定痛阈后每组随机取6只大鼠取L4-6脊髓组织,逆转录PCR(RT-PCR)法检测p38MAPK mRNA和BDNF mRNA的表达。结果与S组比较,C组术后1、3、7、14d机械痛阈和热痛阈明显降低,p38MAPK mRNA和BDNF mRNA的表达明显上调(P<0.05);与C组比较,D组术后3、7、14d机械痛阈和热痛阈显著升高,p38MAPK mRNA和BDNF mRNA表达明显下调(P<0.05);与术前比较,C组、D组机械痛阈和热痛阈术后1、3、7、14d显著降低,第7天时降到最低(P<0.05);与术后1d比较,C组、D组p38MAPK mRNA和BDNF mRNA于术后3、7、14d明显升高,第7天达到最高(P<0.05);对p38MAPK和BDNF mRNA的表达进行相关性分析,Pearson相关系数为0.901,表明p38MAPK mRNA和BDNF mRNA表达呈正相关(P<0.05)。结论右美托咪啶对大鼠坐骨神经慢性压迫性损伤疼痛具有明显的镇痛效应,其机制可能与抑制p38MAPK的活化,从而下调BDNF的表达有关。
Objective To investigate the analgesic effects of dexmedetomidine on p38 mitogen-activated protein kinase（p38MAPK）and brain-derived neurotrophic factor（BDNF）mRNA expression in the spinal cord of rats with sciatic nerve chronic constriction injury（CCI）-induced neuropathic pain.Methods Seventy-two male SD rats were randomly divided into 3 groups（n=24 each）：sham operation group（group S）,CCI group（group C）,dexmedetomidine group（group D）.In group S the right sciatic nerve was exposed but not ligated,and in group C and group S four ligatures were placed around the right sciatic nerve.From the instant after operation 50 μg/kg of dexmedetomidine was injected separately and intraperitoneally into group D daily,and respectively the same volume normal saline was injected into group S and group C.Mechanical and thermal pain threshold was measured by paw withdrawal latencies at 1 d before operation and the 1,3,7,14 d after operation.After the measurement of pain threshold at 1,3,7,14 d after operation,the L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK and BDNF mRNA by reverse transcription-polymerase chain reaction（RT-PCR）.Results Mechanical and thermal pain threshold was markedly reduced at 1,3,7,14 d after operation,and p38MAPK and BDNF mRNA expression was significantly up-regulated in group C as compared with group S（P0.05）;Compared with group C the mechanical and thermal pain threshold was significantly increased at the 3,7,14 d after operation,and p38MAPK and BDNF mRNA expression was markedly down-regulated in group D（P0.05）;In group C and group D the mechanical and thermal pain threshold was significantly reduced at 1,3,7,14 d after operation as compared with before operation,and to a minimum at the 7 d after operation（P0.05）;Compared with 1 d after operation,the p38MAPK and BDNF mRNA in group C and group D was significantly increased at the 3,7,14 d after operation,and to the highest at the 7 d after operation（P0.05）;The correlation analysis on p38MAPK mRNA and BDNF mRNA revealed the Pearson correlation coefficient was 0.901,suggesting a strong positive correlation between p38MAPK mRNA and BDNF mRNA（P0.05）.Conclusion Dexmedetomidine showed an obvious analgesic effects on CCI of rats,which was possibly mediated via the decrease of p38MAPK,and down-regulati on of BDNF expression in the spinal cord.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2012年第6期670-674,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
