胰岛素与尼莫地平对大鼠基底前脑胆碱能神经元及空间学习记忆的影响  

Effects of insulin and nimodipine therapy on cholinergic neurons in the basal forebrain as well as on the learning and memory of streptozotocin-diabetic rats

作　　者：李文超[1] 郭灵[2] 

机构地区：[1]解放军第303医院门诊部 [2]广西医科大学人体解剖学教研室,广西南宁530021

出　　处：《局解手术学杂志》2012年第3期248-251,共4页Journal of Regional Anatomy and Operative Surgery

基　　金：广西自然科学基金项目(桂科自0542069)

摘　　要：目的探讨胰岛素与尼莫地平对基底前脑胆碱能神经元与学习记忆在1型糖尿病脑病发生中的影响。方法将成年雄性Wistar大鼠随机分成糖尿病组、干预组、载体组及正常对照组。用链脲佐菌素成功建立成1型糖尿病模型12周后,对干预组大鼠每日皮下注射长效胰岛素(3 IU)、腹腔注射尼莫地平(20 mg/kg),连续用药6周,在相同条件下对载体组大鼠注射等体积的无药物液体,但对糖尿病组或正常对照组大鼠未进行任何处理。应用Morris水迷宫及胆碱乙酰转移酶(ChAT)免疫组化方法,分别测定各组大鼠的空间学习记忆能力及基底前脑胆碱能神经元的变化。结果糖尿病组大鼠内侧隔核、斜角带核垂直支、斜角带核水平支的ChAT阳性神经元数均明显减少(P<0.05),空间学习记忆能力也明显下降(P<0.05);干预组大鼠以上三个核团的ChAT阳性神经元数与学习记忆能力均明显大于糖尿病组大鼠(P<0.05),但干预组的各项指标仍然明显低于载体组大鼠或正常对照组大鼠(P<0.05)。结论在糖尿病的长期自然发展过程中,若不进行治疗则可累及到基底前脑胆碱能神经元,导致学习记忆障碍,这可能是引发1型糖尿病脑病的一个负性因素;此时联合应用胰岛素与尼莫地平仍可有效遏制该脑病向纵深发展的恶性势头。Objective To explore the influence of insulin and nimodipine on basal forebrain cholinergic neurons and learning memory in type 1 diabetic encephalopathy.Methods Thirty-two male Wistar rats were randomly divided into four groups（eight rats for each group）：diabetes group,intervention group,vector group and control group.Twelve weeks after establishing the model with STZ,insulin（3 IU/kg,subcutaneous injection） and nimodipine（20 mg/kg,intraperitoneal injection） were daily given to each rat in intervention group for 6 weeks consecutively while rats in the vector group were injected the same amount of liquid without drug.And rats in diabetes group and control group were out of any treatment.Morris water maze and immunohistochemistry for choline acetyltransferase（ChAT） were used to detect the change of the cognitive activities and cholinergic neurons in the basal forebrain of rats in four groups.Results Both the abilities of spatial learning and memory and the number of ChAT immunoreactive（ChAT-IR） neurons in MS,vDB and hDB of rats in diabetes group were the weakest or the smallest separately in the four groups（P0.05）.The parameters above in intervention group became significantly larger than those in diabetes group（P0.05）.But they were still much lower than those both in vehicle group and control group（P0.05）.Conclusion The data indicated that the obvious decreases in the number of cholinergic neurons in the basal forebrain may related to impairments in spatial learning and memory.The combined utilization of insulin and nimodipine is capable of preventing the deterioration of the encephalopathy.

关 键 词：糖尿病脑病 基底前脑 胆碱能神经元 胰岛素 尼莫地平 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]