激活γ-氨基丁酸B型受体对糖尿病神经痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白和N-甲基-D-天冬氨酸受体2B亚基表达的影响  

Effect of activating T-aminobutyric acid B receptors on the exprssion of phosphorylated cycliic a- denosine monophosphate response element binding protein and N-methyl-D-aspartate receptor sub-unit 2B in the spinal dorsal horn in rats with diabetic neuropathic pain

作　　者：刘朋[1] 郭闻亚[2] 赵晓南[1] 吕艳霞[1] 魏淑明[1] 王秀丽[1] 

机构地区：[1]河北医科大学第三医院麻醉科,石家庄050051 [2]河北医科大学,石家庄050051

出　　处：《中华实验外科杂志》2013年第2期373-376,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30772082）;河北省自然科学基金资助项目（C2008000931）;河北省卫生厅资助课题（GL2011-46、20100105）

摘　　要：目的利用1-氨基丁酸B型受体（GABA。）受体激动剂（巴氯芬）和拮抗剂（CGP55845），探讨激活GABA。受体对糖尿病神经痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）和N-甲基-D-天冬氨酸：受体2B亚基（NMDA4B、NR2B）表达的影响。方法6，2只SD雄性大鼠随机分为两组：正常对照组（C组）和糖尿病神经痛模型组（D组），腹腔分别注射生理盐水或链脲佐菌素（STZ，60mg／kg）。50只大鼠腹腔注射STZ，4周后36只大鼠成功制备成糖尿病神经痛（DNP）模型并鞘内置管，根据鞘内给药（共20u1）随机分为3组（m=12）：DNP对照组（D1组）：生理盐水10ul＋生理盐水10ul；巴氯芬组（D2组）：生理盐水10u1＋巴氯芬0．5ug；CGP5845＋巴氯芬组（D3组）：CGP5584510ug＋巴氯芬0．5ug；12只同周龄正常大鼠腹腔注射生理盐水并鞘内置管作为C组，鞘内注射生理盐水10ul＋生理盐水10ul。4组大鼠两次鞘内注射间隔15min，连续4d，每天鞘内注射前、后30min测定大鼠50％机械缩足阈值（PwT），各时点分别为：T1、T2、13、T4，最后1次测完后取大鼠脊髓背角，采用分子生物学方法测定p-CREB、环磷酸腺苷反应元件结合蛋白（CREB）和NR2B受体表达变化。结果与C组比较，D1、D3两组大鼠T1-T4各时点PwT明显降低（P〈0．05），p-CREB和NR2B蛋白表达及NR2BmRNA表达明显增多（P〈0．05）；与D1组比较，D2组大鼠各时点PwT显著升高（P〈0．05）；与D1组p-CREB（0．76±0．13）、NR2B（1．28±0．14）蛋白表达、NR2BmRNA表达（0．83±0．10）比较，D2组p-CREB（0．45±0．08）和NR2B（0．88±0．13）蛋白表达及NR2BmRNA表达（O．53±0．08）显著降低（P〈0．05）。4组间比较，CREB蛋白表达差异无统计学意义（P〉0．05）。结论激活GABA。受体可使糖尿病神经痛大鼠脊髓背角p-CREB、NR2B蛋白表达下调，抑制糖尿病神经痛。Objective To investigate the effect of activating y-aminobutyric acid（ GABAB ） recep- tors on the expression of phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） and N-methyl-D-aspartate receptor subunit 2B （NR2B） receptors in the spinal dorsal horn in rats with diabetic neuropathic pain （DNP） by using GABAB receptors agnnist （baclofen） and atagonist （CGP55845）. Methods Sixty-two male SD rats were randomly divided, into two groups：： normal control group （C group） and DNP model group （D group）, which were intraperitonealy injected with saline and streptozocin （STZ） respectively. Fifty rats were intraperitonealy injected with STZ （60 nag/kg）, and 4weeks later, DNP models were successfully established in 36 rats which were randomly divided into 3 groups （n = 12 each） according to the iinjected medicines： saline 10 Ixl ＋ saline 10 ILl were injected in- tratheeally in D1 group, saline 10 gl ＋ baclofen 0. 5 ug in D2 group, CGP55845 10 ug ＋ baclofen 0. 5ug in D3 group. Saline 10 bd ± sadine 10 pj were injected intratheeally in 12 normal rats as C group. There was an interval of 15 rain between twice intratheeal injections in four groups. The PWT was measured at 30 rain before and after intrathecal injection for 4 days, and the time points were as follows ： T1, T2, T3 and T4. The spinal cord dorsal horns of rats were removed after measurement of PWT for detection of the expression of p-CREB, cyclic adenosine monophosphate response element binding protein （ CREB ） and NR2B receptor. Results As compared with C group, the expression levels of NR.2B and p-CREB protein were significantly inereased, while PWT was significantly decreased at each time point （TI-T4） in D1 and D3 groups （P〈0.05）. As compared with D1 group [p-CREB protein （0.76 ±0. 13）, NR2B protein （1.28 ±0. 14）, and NR2B mRNA （0.83 ± 0. 10） ], the protein expression levels of NR2B （0. 88±0. 13） and p-CREB （0. 45 ±0.08） and NR2B m

关 键 词：糖尿病 疼痛 y-氨基丁酸受体 环磷酸腺苷反应元件结合蛋白 N·甲基-D-天冬氨酸受体 

分 类 号：R74[医药卫生—神经病学与精神病学] R587[医药卫生—临床医学]