摘要
目的评价氯胺酮对糖尿病神经痛并发抑郁大鼠海马γ-氨基丁酸B1（GABAB1）受体及脑源性神经生长因子（BDNF）蛋白表达的影响。方法清洁级雄性sD大鼠60只，体重180～200g，采用腹腔注射链脲佐菌素联合强迫游泳实验的方法制备大鼠糖尿病神经痛并发抑郁模型，取模型制备成功的大鼠40只，采用随机数字表法，将其分为2组（n=20）：模型对照组（Ns组）和氯胺酮组（K组）。K组肌肉注射氯胺酮10mg／kg（O．5m1），1次／d，持续1周。Ns组以等容量生理盐水替代。另取20只大鼠为正常对照组（C组）。于给药完成后第1天（T1）和第2周（T2）时，测定大鼠机械缩足反应阈（MWT）及记录强迫游泳实验不动时间（IMFST），测定结束后取海马，采用免疫组织化学法和Westernblot法测定海马GABA。受体及BDNF蛋白的表达水平，采用RT．PCR法检测海马GABAB1受体及BDNFmRNA的表达水平。结果与C组比较，NS组MWT降低，IMFST延长，海马GABA。受体和BDNF蛋白及其mRNA表达下调（P〈0．05）。与NS组比较，K组MWT升高，IMFST缩短，海马GABA。受体及BDNF蛋白及其mRNA的表达上调（P〈0．05）。结论氯胺酮可通过上调糖尿病神经痛并发抑郁大鼠海马GABA。受体及BDNF蛋白的表达，减轻神经病理性痛和抑郁状态。
Objective To evaluate the effects of ketamine on the expression of gamma-aminobutyric acid type B receptor subunit 1 （GABAB1） receptors and brain-derived neurotrophic factor （BDNF） in rats with diabetic neuropathic pain （DNP） complicated with depression. Methods Pathogen-free male Sprague-Dawley rats, weighing 180-200 g, were used in the study. The model of DNP was established by intraperitoneal injection of streptozocin, and then depression was induced by forcing the rats to swim in a narrow cylinder from which they cannot escape. Forty rats with DNP complicated with depression were randomly divided into 2 groups （ n = 20 each） using a random number table： model control group （NS group） and ketamine group （K group）. In group K, ketamine 10 mg/kg （0.5 ml） was injected intramuscularly once a day for one week. In NS group, the equal volume of normal saline was given instead of ketamine. Another 20 rats were used as normal control group （ C group）. Mechanical paw withdrawal threshold to von Frey stimuli （MWT） was measured and the time for immobility during forced swimming test was recorded at 1 day after completion of administration （T1） and 2nd week after completion of administration （T2）. After the end of behavior test, the hippocampi of rats were removed for detection of GABAB1 receptor and BDNF expression （using immunohistochemistry and Western blot） and expression of GABAB1 receptor and BDNF mRNA （using RT-PCR）. Results Compared with C group, MWT was significantly decreased, the time for immobility during forced swimming test was prolonged, and the expression of GABAsl receptor and BDNF protein and mRNA was down-regulated in group NS. Compared with group NS, MWT was significantly increased, the time for immobility during forced swimming test was shortened, and the expression of GABABI receptor and BDNF protein and mRNA was up-regulated in group K. Conclusion Ketamine can up- regulate the expression of GABAB1 receptor and BDNF in rats with DNP complicated wit
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第6期696-700,共5页
Chinese Journal of Anesthesiology
基金
国家自然科学基金（81371231）
河北省自然科学基金（H2013206087）
河北省卫生厅资助课题（GL2011-46,20100105）
