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

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。

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

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 APP5-165 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 APP5-165 can reverse this change.