CAJ | 학술논문

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 ～ 200 g,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10 mg/kg(0.5 ml),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GABAB1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GABAB1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GABAB1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GABAB1受体及BDNF蛋白的表达,减轻神经病理性痛和抑郁状态.
목적 평개록알동대당뇨병신경통병발억욱대서해마γ-안기정산B1(GABAB1)수체급뇌원성신경생장인자(BDNF)단백표체적영향.방법 청길급웅성SD대서60지,체중180 ～ 200 g,채용복강주사련뇨좌균소연합강박유영실험적방법제비대서당뇨병신경통병발억욱모형,취모형제비성공적대서40지,채용수궤수자표법,장기분위2조(n=20):모형대조조(NS조)화록알동조(K조).K조기육주사록알동10 mg/kg(0.5 ml),1차/d,지속1주.NS조이등용량생리염수체대.령취20지대서위정상대조조(C조).우급약완성후제1천(T1)화제2주(T2)시,측정대서궤계축족반응역(MWT)급기록강박유영실험불동시간(IMFST),측정결속후취해마,채용면역조직화학법화Westernblot법측정해마GABAB1수체급BDNF단백적표체수평,채용RT-PCR법검측해마GABAB1수체급BDNFmRNA적표체수평.결과 여C조비교,NS조MWT강저,IMFST연장,해마GABAB1수체화BDNF단백급기mRNA표체하조(P＜0.05).여NS조비교,K조MWT승고,IMFST축단,해마GABAB1수체급BDNF단백급기mRNA적표체상조(P＜0.05).결론 록알동가통과상조당뇨병신경통병발억욱대서해마GABAB1수체급BDNF단백적표체,감경신경병이성통화억욱상태.
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 GABAB1 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 GABAB1 receptor and BDNF protein and mRNA was up-regulated in group K.Conclusion Ketamine can upregulate the expression of GABAB1 receptor and BDNF in rats with DNP complicated with depression,thus mitigating DNP and depressed state.