中文摘要：

目的 利用γ-氨基丁酸B型受体（GABAB）受体激动剂（巴氯芬）和拮抗剂（CGP55845）,观察作用GABAB受体对糖尿病神经痛合并抑郁大鼠海马脑源性神经生长因子（BDNF）表达的影响.方法 将100只雄性SD大鼠随机分为两组,正常对照组（C组）20只和糖尿病神经痛合并抑郁模型组（D组）80只,分别腹腔注射生理盐水或链脲佐菌素（STZ,60 mg/kg）.结合强迫游泳实验,3周后,D组大鼠模型制备成功.两组大鼠均行鞘内置管.根据鞘内给药不同将D组大鼠随机分为4组（n=20）：D1组：生理盐水10 μl＋生理盐水10μl;D2组：巴氯芬0.5 μg＋生理盐水10 μl; D3组：CGP55845 10 μg＋生理盐水10 μl; D4组：CGP55845 10 μg＋巴氯芬0.5 μg.C组：生理盐水10μl＋生理盐水10μl.5组大鼠2次鞘内注药间隔15 min,连续4d,分别于第4天给药完成后2 h（T1）、给药完成后2周（T2）测定50％缩足阈值（PWT）和强迫游泳实验不动时间（IMFST）,并在T1、T2时间点每组大鼠取海马组织,采用免疫组织化学法和分子生物学方法测定BDNF表达变化.结果 与C组比较,D组各时间点PWT明显降低[（13.02±1.68）g比（3.46±0.84）g,P＜0.05],IMFST明显延长[（47.14 ±3.65）s比（178.12±12.49）s,P＜0.05],BDNF阳性细胞数减少[（34.10±3.37）个比（16.50±2.41）个,P＜0.05],其mRNA（0.93 ±0.04比0.52±0.09,P＜0.05）及蛋白（1.09±0.06比0.56 ±0.09,P＜0.05）表达显著下降.与D1组比较,D2、D3组大鼠各时间点IMFST明显缩短（P＜0.05）、BDNF表达明显增多（P＜0.05）,D2组大鼠各时间点PWT显著升高（P＜0.05）,而D3组PWT无明显变化（P ＞0.05）;D4组与D1组比较,各项指标无显著变化（P＞0.05）.上述指标各组T1与T2时间点比较均无明显变化（P＞0.05）.结论 激活或阻断GABAB受体均可通过上调海马组织BDNF表达,改善糖尿病神经痛大鼠的抑郁状态.

英文摘要：

Objective To investigate the effect γ-aminobutyric acid B （GABAB） receptors on the expression of brain-derived neurotrophic factor （BDNF） in rats with diabetic neuropathic pain （DNP） with depression by using GABAB receptors agonist （baclofen） and antagonists （CGP55845）.Methods 100 male SD rats were randomly divided into two groups：normal control group （C group） and DNP with depression model group （D group）,in which the rats were intraperitonealy injected with saline or streptozocin （STZ） respectively.The DNP with depression models were established in 80 rats three weeks after the forced swimming test （FST）,and 80 rats were randomly divided into 4 subgroups （n =20,each group） according to the given medicines：saline 10 μl ＋ saline 10 μl injected intrathecally in D1 group,baclofen 0.5 μg ＋ saline 10 μl in D2 group,CGP55845 10 μg ＋ saline 10 μl in D3 group,and CGP55845 10 μg ＋baclofen 0.5 μg in D4 group.Saline 10 μl ＋ saline 10 μl were injected intrathecally in 20 normal rats （C group）.There was an interval of 15 min between twice intrathecal injections in five groups for 4 days.The paw withdrawal threshold （PWT） and immobility time of FST （IMFST） were measured two h （T1） and two weeks after intrathecal injection （T2） respectively.The hippocampi of rats were removed after measurements of PWT and IMFST for detection of BDNF expression.Results As compared with C group,the PWT was significantly reduced [（13.02 ± 1.68） g vs.（3.46 ±0.84） g,P 〈0.05],the IMFST was significantly prolonged [（47.14 ±3.65） s vs.（178.12 ± 12.49） s,P 〈0.05],and the expression of BDNF was decreased （P 〈 0.05） in D group.As compared with D1 group,the IMFST was significantly shortened （P 〈 0.05） in D2 and D3 groups,the expression of BDNF was increased （P 〈 0.05） in D2 and D3 groups,and the PWT was significantly increased （P 〈 0.05） in D2 group but showed no significant change in D3 group.The PWT,IMFST and expression of