中文摘要：

目的：探讨持续高血糖对大鼠海马颗粒下区（subgranular zone，SGZ）神经干细胞状态的影响及可能机制。方法：SD大鼠注射链脲佐菌素（streptozotocin，STZ）诱导1型糖尿病模型，腹腔注射5-溴脱氧尿嘧啶核苷（bromodeoxyuridine，BrdU）标记新生细胞。利用免疫组化法检测海马SGZ区Ki67，5-溴脱氧尿嘧啶核／双皮质素（bromodeoxyuridine／doublecortin，BrdU／DCX）标记的阳性细胞。利用免疫印迹法检测海马胰岛素受体B（insulin receptorβ，IRβ），糖元合成酶激酶3B（pho-glycogen synthase kinase-3β，GSK313），β-链蛋白（13-Catenin）表达水平。结果：STZ注射大鼠胰岛素降低，血糖升高；糖尿病大鼠海马区Ki67阳性细胞，BrdU／DCX阳性细胞和对照组比较明显减少，海马区IRβ，pho—GSK3β，β-Catenin表达水平和对照组比较显著下降（P〈0．05）。结论：STZ诱导的1型糖尿病大鼠海马SGZ区新生细胞增值能力下降，细胞分化异常，这一变化和海马区胰岛素信号下调，GSK313活化，B-Catenin降解增加有关。

英文摘要：

Objective： To investigate the status of adult neural stem cells in SGZ of hippocampus and its regulated mechanisms under persistent hyperglycemia induced by streptozotocin （STZ） injection. Methods： Male SD rats were injected once with 0.065 g/kg STZ through the femoral vein to induce diabetes. After 2 months, the rats were injected with BrdU （0.60 g/kg, i. p） before sacrificed, and their brains were removed and prepared as needed. Changes in the proliferation and differentiation abilities of the SGZ progenitor cells were determined through immunohistochemistry of Ki67 and BrdU/DCX. The levels of insulin receptors, glycogen synthase kinase 3 β （ GSK3 β）/phospho-GSK3 β, and β-Catenin in the hippocampus were measured by Western Blot. Results： STZ injection caused hypoinsulinaemia and hyperglycemia in diabetic rats. The number of Ki67-positive cells was lower in the SGZ of the diabetic rats than that of age-matched normal rats. The number of BrdU ＋/DCX ＋ cells decreased significantly in the diabetic rats. Furthermore, insulin receptor expression was downregulated in the hippocampus of the diabetic rats. GSK3β phosphorylation and β-Catenin expression decreased in the hippocampus of the diabetic rats （ P 〈 0.05 ）. Conclusion： These results indicated that diabetes caused insulin deficiency, which activated the GSK3β signal by inhibiting 9-1ysine phosphorylation. The negative regulation of GSK3 β decreased the accumulation of β-Catenin. These signals pathways contributed to the deficit of proliferation and dif- ferentiation of adult neural stem cell in hippocampal SGZ in the diabetic rat.