胰岛素抑制Ⅰ型糖尿病模型大鼠脑斜角带核细胞凋亡及学习记忆障碍

Insulin Inhibits Cell Apoptosis in the Diagonal Band of Broca and Cognitive Impairment of Streptozotocin-induced Type 1 Diabetes Rats

目的探索在胰岛素替代治疗下,Ⅰ型糖尿病模型大鼠基底前脑的斜角带核垂直支(VDB)、斜角带核水平支(HDB)凋亡基因Bax与抗凋亡基因Bcl-2表达、细胞凋亡、学习记忆的变化及其相互联系。方法雄性Wistar大鼠随机分成正常组、糖尿病组、胰岛素组、溶剂组。腹腔注射链脲佐菌素来建立Ⅰ型糖尿病模型;以Morris水迷宫检测大鼠的空间记忆能力;免疫组织化学技术检测Bax与Bcl-2的表达;TUNEL染色检测细胞凋亡。结果糖尿病模型大鼠空间记忆能力显著低于正常大鼠;VDB和HDB的Bax蛋白表达显著增加,而Bcl-2蛋白表达显著减少,细胞凋亡数明显增多;而胰岛素处理能显著改善糖尿病模型大鼠的空间记忆能力,翻转VDB和HDB的Bax蛋白及Bcl-2蛋白的异常表达,减少细胞凋亡。结论胰岛素抑制Ⅰ型糖尿病模型大鼠模型大鼠脑斜角带核细胞凋亡并改善学习记忆障碍。

Objective To explore the effects of insulin therapy on impairments of learning and memory,on cell apoptosis,and on Bax or Bcl-2 protein expression in the diagonal band of Broca( vertical limb of diagonal band,VDB; horizontal limb of diagonal band,HDB) of rats with type 1 diabetes. Methods Male Wistar rats were randomly divided into four groups: normal,diabetes,insulin,and vehicle. Type 1 diabetes rat model was established by a dosage of intraperitoneal injection of streptozotocin. Morris water maze was used to investigate spatial memory ability. Immunohistochemistry was used to investigate protein expression of Bax and Bcl-2. Terminal-deoxynucleotidy-transferase-mediated-d UTP nick and labeling( TUNEL) was used to investigate cell apoptosis. Results The spatial memory abilities of rats in the type 1 diabetes group was significantly worse than that of normal rats. The protein expression of Bax in VDB or HDB was significantly increased; while the protein expression of Bcl-2 significantly decreased. However,insulin treatment significantly improved the spatial memory abilities of diabetic rats,reversed the abnormal protein expression of Bax and Bcl-2 in VDB and HDB,and reduced cell apoptosis. Conclusion Insulin can inhibit cell apoptosis in the diagonal band of Broca and cognitive impairment of streptozotocin-induced type 1 diabetes.