链脲佐菌素对大鼠海马p-CREB表达的影响及APP5肽类似物165的治疗作用  

Effect of Streptozotocin on the Expression of Hippocampal p-CREB in Rats and Protection of APP5 Peptide Analog 165 on Rats

作　　者：雷亚平[1] 崔艳君[2] 王蓬文[1] 王蓉[3] 盛树力[3] 田金洲[1] 

机构地区：[1]北京中医药大学东直门医院临床药理实验室 [2]首都医科大学病理教研室,北京100069 [3]教育部神经变性病学重点实验室,北京100053

出　　处：《中国神经免疫学和神经病学杂志》2007年第4期187-190,I0002,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家重点基础研究发展"973"计划基金资助项目(2003CB517104)

摘　　要：目的探讨链脲佐菌素(streptozotocin,STZ)对大鼠海马磷酸化环磷腺苷反应成分结合蛋白(phosphatedcylinc AMP response element binding protein,p-CREB)表达的影响以及APP5肽类似物165的治疗作用。方法将42只Wistar大鼠随机分为对照组、模型组和APP5肽类似物165治疗组。将STZ溶解于人工脑脊液,新鲜配制成浓度为25mg/mL,分别于第1、3天按体重3mg/kg行双侧脑室注射。APP5肽治疗组于3周后开始行APP5肽类似物165灌胃,连续4周。对照组和模型组则以等量生理盐水灌胃。4周后取脑组织海马行免疫组织化学染色和Western-blotting检测p-CREB。结果模型组p-CREB阳性神经细胞数(137.44±22.62)较对照组(27.33±9.91)明显增多(P<0.05),胞质淡染;APP5肽治疗组p-CREB阳性神经元数目(29.78±10.72)与对照组比较差异无统计学意义(P>0.05)。模型组海马p-CREB表达多于对照组和APP5肽治疗组,APP5肽治疗组与对照组接近。结论脑室注射小剂量STZ可使海马p-CREB阳性神经元表达增多,而APP5肽类似物165可使p-CREB阳性神经元表达恢复至正常水平。Objective To investigate the effect of streptozotocin on the expression of hippocampal p-CREB in rats and the protection of APP5 peptide analog 165（APP5-165）. Methods Forty-two Wistar rats were randomly divided into three group： control group, model group and APP5 peptide analog 165 treatment group. Adult wistar rats were injected with intracerebroventricular （i. c. v） streptozotocin （3 mg/kg） bilaterally and stereotaxically. The rats were treated with streptozotocin twice on day 1 and on day 3. Rats in APP5-165 treatment group were adminstered by stomach tube with APPS-165 for 4 weeks, once a day. Then p-CREB in the hippocampus was tested by immunhistochemical stain and Western-blotting. Results The number of p-CREB positive cells in the hippocampus of model group was much more than those of control group （P〈0.05）. In contrast, the number of p-CREB positive cells in the hippocampus of the control group was similar to that of APP5 group. The expression of p-CREB of in the hippocampus of model group was increased and APP5-165 could rehabilitate the abnormal expression of p-CREB showed by Western-blotting. Conclusions Streptozotocin administered i. c. v can lead to the increased expression of p-CREB positive cells in the hippocampus, while APPS- 165 can reverse this change.

关 键 词：链脲佐菌素 P-CREB APP5肽类似物165 海马 老年性痴呆 

分 类 号：R749.1[医药卫生—神经病学与精神病学]