褪黑素对1型糖尿病脑病大鼠学习记忆和海马齿状回细胞凋亡及Bax与Bcl-2蛋白表达的影响  

Effect of melatonin on learning and memory as well as cell apoptosis and Box or Bcl-2 protein expression in the hippocampal dentate gyrus of rat with type 1 diabetic encophalopathy

作　　者：玉洪荣[1] 王薇[1] 郭灵[1] 张芳[1] 蓝玲[1] 白鹭[1] 

机构地区：[1]广西医科大学人体解剖学教研室,广西南宁530021

出　　处：《解剖学研究》2009年第2期94-98,共5页Anatomy Research

基　　金：广西科学基金(桂科自0542069)

摘　　要：目的探讨褪黑素治疗对1型糖尿病脑病空间学习忆忆、海马齿状回细胞凋亡以及凋亡相关基因Bax与Bcl-2蛋白表达的影响。方法将成年健康雄性Wistar大鼠随机分成4组(每组均为12只大鼠):1型糖尿病脑病组、载体模型治疗组、褪黑素治疗组、正常对照组。通过腹腔注射链脲佐菌素(55mg/kg,溶于柠檬酸缓冲液中),建立1型糖尿病脑病模型;通过对该脑病模型大鼠腹腔注射褪黑素(200μg/kg,溶解于乙醇生理盐水中),建立褪黑素治疗模型;分别通过对大鼠腹腔注射等体积的柠檬酸缓冲液、乙醇生理盐水,建立载体治疗模型;但未对正常对照组大鼠进行过任何处理。应用Morris水迷宫、Bax、Bcl-2、TUNEL反应技术,观察各组大鼠空间学习记忆、海马齿状回的颗粒下区(SGZ)和颗粒细胞层(GCL)的细胞凋亡及Bax与Bcl-2基因的蛋白表达程度。结果1型糖尿病脑病大鼠在水迷宫的逃避潜伏期和游泳距离均比其它各组的对应指标明显延长(P<0.01),该脑病组大鼠海马齿伏回的SGZ和GCL的Bax阳性细胞数、TUNEL阳性细胞数也均比其它各组的对应指标明显升高(P<0.01),但该脑病组SGZ和GCL的Bcl-2阳性细胞数则明显低于其它各组的相应指标(P<0.01)。应用褪黑素治疗该脑病组大鼠30d后,可将1型糖尿病脑病组大鼠的以上各项指标逆转至接近正常水平(P<0.01)。结论褪黑素治疗不仅可纠正因1型糖尿病脑病大鼠海马齿状回凋亡基因Bax和抗凋亡基因Bcl-2蛋白质表达水平比例异常而引发的细胞凋亡,还可改善该脑病的空间学习记忆障碍,提示褪黑素在防治该脑病中具有一定的功效。Objective To examine the effects of melatonin administration on learning and memory as well as on cell apoptosis and on Bax or Bcl-2 protein expression in the hippocampal dentate gyrus of rat with type 1 diabetic encephalopathy. Methods Model of type 1 diabetic encephalopathy rats was made by intraperitoneal injection of a dosage of streptozotocin. After 5 days of successful establishment of the model,melatonin （200μg/kg） was intraperitoneally injected into each encephalopathy model rat for 30 consecutive days. Morris water maze, terminal-deoxynucleotidyl-transferase-mediated-dUTP nick and labeling （TUNEL） technique, Bax and Bcl-2 immunohistochemistry were used to investigate the behaviors and cell apoptosis in the subgranular zone （SGZ） and granular cell layer （GCL） of the hippoeampal dentate gyrns of each rat. Results The abilities in learning and memory of type 1 diabetic encephalophathy rats were significantly weaker than those in the control group rats （P〈 0.01）. Moreover, the numbers of Bax immunoreactive （Bax-IR） cells and TUNEL-positive cells in SGZ or GCL of encephalopathy group rats were significantly larger than those in control group rats（P〈O.01 ）; while the number of Bcl-2 IR cells of encephalopathy group rats was significantly smaller than that of control group rats （P〈0.01）. However, after 30 days of melatonin treatment, the above parameters showed by encephalopathy group rats were reversed to the normal levels （P〈0.01）. Conclusion Melatonin treatment may exert a negative effect on the cell apoptosis by mediation of Bax or Bcl-2 gene expression, resulting in improvement of spatial learning and memory of type 1 diabetic encephalopathy. The above data indicate that melatonin is a potential drug for preventing and treating the diabetic encephalopathy.

关 键 词：褪黑素 糖尿病脑病 1型糖尿病 学习记忆 细胞凋亡 BAX Bcl-2 齿状回 海马 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]