摘要
目的探讨米贝拉地尔对糖尿病神经病理性疼痛模型大鼠p38丝裂原活化蛋白激酶(p38MAPK)信号通路的影响。方法用链脲佐菌素腹腔注射建立糖尿病神经病理性疼痛大鼠模型。按随机数表法将造模成功SD大鼠分为模型组、对照组和低、中、高3个剂量实验组,每组14只;另取13只正常大鼠作为正常组。模型组和正常组大鼠腹腔注射0.9%NaCl;对照组腹腔注射4 mg·mL^-1加巴喷丁溶液10 mL·kg^-1;低、中、高3个剂量实验组腹腔注射0.25,1.0,2.0 mg·mL^-1米贝拉地尔溶液10 mL·kg^-1,1次/天,连续干预14 d。用测痛仪测定机械性缩足反射阈值(MWT),用原位末端标记法测定背根神经节神经细胞凋亡率,用蛋白免疫印迹法测定背根神经节磷酸化p38MAPK(p-p38MAPK)相对表达水平(灰度值)。结果正常组、模型组、对照组和低、中、高3个剂量实验组在14 d的MWT分别为(52.01±4.77),(27.24±2.53),(48.73±4.02),(35.01±2.86),(40.62±3.45)和(48.51±3.97)g;这6组的细胞凋亡率分别为(1.76±0.24)%,(8.85±0.62)%,(5.07±0.39)%,(7.73±0.56)%,(6.98±0.44)%和(5.01±0.36)%;这6组的p-p38MAPK相对表达量分别为0.42±0.06,1.60±0.19,0.71±0.08,1.43±0.16,1.05±0.14和0.74±0.06。上述指标:正常组与模型组比较,差异均有统计学意义(均P<0.05);对照组和低、中、高3个剂量实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论米贝拉地尔能明显提高糖尿病神经病理性疼痛模型大鼠痛阈,减轻疼痛,且呈剂量依赖性,其作用可能与抑制脊髓及背根神经节p38MAPK信号通路、减少神经细胞凋亡有关。
Objective To study the effect of mibefradil on p38 mitogen activated protein kinase(p38 MAPK)signaling pathway in diabetic neuropathic pain rats.Methods The model building group was established diabetic neuropathic pain model by intraperitoneal injection of streptozotocin.Successful modeling SD rats were divided into 5 groups according to random number table:model group,control group,and experimental-L,experimental-M,experimental-H groups,14 rats in each group.Another 13 normal rats were taken as the normal group.Rats in model group and normal group were given physiological saline;control group was given 4 mg·mL^-1 gabapentin solution 10 mL·kg^-1 by intra-peritoneal injection,qd;experimental-L,experimental-M,experimental-H groups were given 0.25,1.0,2.0 mg·mL^-1 mibefradil solution 10 m L·kg^-1 by intraperitoneal injection,respectively,once a day for 14 days.The mechanical withdrawal threshold(MWT)was measured by a painkiller.The apoptotic rate of dorsal root ganglion neurons was measured by terminal deoxynucleotidyl transferase mediated d UTP nick end labeling method.The relative expression(grey value)of phosphorylated p38 MAPK(p-p38 MAPK)in dorsal root ganglion was determined by Western blot method.Results The MWT at 14 d in normal group,model group,control group,and experimental-L,experimental-M,experimental-H groups were respectively(52.01±4.77),(27.24±2.53),(48.73±4.02),(35.01±2.86),(40.62±3.45)and(48.51±3.97)g;the apoptosis rate in the six groups were respectively(1.76±0.24)%,(8.85±0.62)%,(5.07±0.39)%,(7.73±0.56)%,(6.98±0.44)%and(5.01±0.36)%;p-p38 MAPK in the six groups were respectively 0.42±0.06,1.60±0.19,0.71±0.08,1.43±0.16,1.05±0.14 and 0.74±0.06.Comparison between model group and normal group,the difference of the factors were significantly(all P<0.05);comparison between control group,experimental-L,experimental-M,experimental-H groups and model group,the difference of the factors were significantly(all P<0.05).Conclusion Mibefradil can significantly increase the pain threshold of
作者
姚杰
邢珍
滕金亮
高艳
刘斐
崔大鹏
庞茜茜
郭颖
YAO Jie;XING Zhen;TENG Jin-liang;GAO Yan;LIU Fei;CUI Da-peng;PANG Qian-qian;GUO Ying(Department of Anesthesiology,First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Intensive Medicine,First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Hepatobiliary Surgery,First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Pharmaceutical Sciences,First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Pathology,Hebei North University,Zhangjiakou 075000,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第2期177-180,共4页
The Chinese Journal of Clinical Pharmacology
基金
河北省医学科学研究重点课题计划基金资助项目(20170778)。
