海马sortilin在链脲佐菌素诱导的糖尿病认知损伤小鼠中的作用

目的 探讨海马sortilin在链脲佐菌素（STZ）诱导的糖尿病认知损伤小鼠中的作用。方法 24只成年雄性ICR小鼠，随机分为溶媒对照组（NS）和实验组（STZ）。STZ腹腔注射诱导糖尿病认知损伤动物模型，注射后用血糖仪检测血糖改变，注射后第8周采用新旧事物识别实验检测各组小鼠认知功能；免疫组织化学方法检测sortilin免疫阳性产物表达变化；Western blotting和Real-time PCR方法检测各组小鼠海马sortilin和脑源性神经营养因子（BDNF）蛋白及mRNA表达变化。结果 与NS组相比，STZ组小鼠空腹血糖显著增高（P<0.01）；在新旧事物识别实验中新事物辨别指数明显降低（P<0.05）；海马区sortilin的免疫阳性产物（P<0.05）、蛋白（P<0.01）以及mRNA（P<0.05）表达均显著下调；海马区BDNF mRNA（P<0.01）及蛋白（P<0.05）表达均明显降低。结论 STZ诱导的糖尿病小鼠认知损伤可能与海马sortilin的表达下调有关。

Role of hippocampal sortilin in streptozocin inducing diabetic cognitive impairment mice

Objective To investigate the role of hippocampal sortilin in streptozotocin( STZ) inducing diabetic cognitive impairment in mice. Methods Twenty four adult male ICR mice were randomly divided into control group( NS group) and experimental group( STZ group). The animal model of diabetic cognitive impairment was induced by STZ treatment. The blood glucose was measured by blood glucose meter every other week. The cognitive function was determined by novelty object recognition test 8 weeks after STZ injection. The expressions of sortilin in hippocampus of mice were determined by immunohistochemistry. The expressions of sortilin and brain-derived neurotrophic factor( BDNF) protein in hippocampus of mice were determined by Western blotting. The expressions of sortilin and BDNF mRNA in hippocampus of mice were determined by Real-time PCR. Results STZ treated mice showed significantly increased blood glucose compared with the NS group( P < 0. 01). Compared with the NS group,the STZ group showed significantly reduced discrimination index in the novelty object recognition test( P<0. 05). The result of immunohistochemistry assay showed that the positive score of NS group was significantly higher than STZ group( P<0. 05).The results of Western blotting and Realtime PCR showed that the expression level of sortilin protein( P<0. 01) and mRNA( P<0. 05) in the hippocampus of STZ group decreased significantly compared with the NS group. The results of Western blotting and Real-time PCR showed that the expression level of BDNF protein( P < 0. 05) and mRNA( P < 0. 01) in the hippocampus of STZ group decreased significantly compared with the NS group. Conclusion The STZ-induced cognitive impairment in mice may be related to the down-regulation of sortilin in the hippocampus.