糖尿病小鼠认知功能及不同时相点硫化氢的表达.docVIP

糖尿病小鼠认知功能及不同时相点硫化氢的表达 戚韵雯，何选丽，朱丽娟，刘梦洁，晏 勇 （400016 重庆，重庆医科大学附属第一医院神经内科，重庆市神经病学重点实验室） ［摘要］ 目的 观察糖尿病(DM)小鼠的认知功能及脑组织内硫化氢（H2S）、胱硫醚-β-合成酶(CBS)的变化。方法 40只C57BL/6J小鼠分为正常组和模型组。通过长期给予小鼠高脂高糖饮食及腹腔注射链脲佐菌素(120mg/kg )诱导2型糖尿病（T2DM）模型。T2DM模型组再分为4、8、12和16周4个时相点。Morris水迷宫实验检测各组小鼠认知改变，敏感硫电极法、免疫组化法测定皮质、海马内H2S水平、CBS活性及蛋白表达等，并进行相关性分析。结果 与正常组相比，4周时T2DM小鼠定位导航实验的潜伏期开始延长(P0.05)，8周时空间探索实验中平台所在象限停留时间百分率开始降低（P0.01）；12、16周时皮质H2S水平、CBS酶活性及CBS蛋白表达均降低(P0.05)；8、12、16周时海马H2S水平、CBS酶活性及CBS蛋白表达均显著减少(P0.01)。相关分析表明，皮质、海马H2S含量及CBS活性与小鼠认知水平正相关。结论 T2DM小鼠脑组织中H2S含量、CBS酶活性及蛋白表达均减少，认知功能下降。推测内源性H2S减少、CBS活性降低可能会引发及加重DM认知功能损害程度。 ［关键词］ 糖尿病；认知功能损害；硫化氢；胱硫醚-β-合成酶 ［中图法分类号］ ［文献标志码］ A Cognitive function and hydrogen sulfide content in diabetic mice Qi Yunwen, He Xuanli, Zhu Lijuan, Liu Mengjie, Yan Yong (Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China) ［Abstract］ Objective To observe the changes of hydrogen sulfide (H2S) and cystathionine-β-synthase (CBS) in brain tissues and cognitive function in diabetic mice. Methods Forty C57BL/6J mice were divided into a normal group and a model group. Mouse models of diabetes mellitus were established by high fat diet with medium dose streptozocin (STZ). Mouse models were subdivided into groups of 4, 8, 12 and 16 weeks. Changes of recognition were tested by Morris water maze. The gas levels of H2S, CBS activity and CBS expression were detected by immunohistochemistry and sensitive sulfur electrode assay. Correlation analysis was conducted. Results Compared to the normal group, the latency of memory of mouse models started to increase at 4 weeks (P0.05), while the percentage of total time left in the target quadrant began to decrease at 8 weeks (P0.01). The gas levels of H2S, CBS activity and CBS expression in the cortex of the model mice at 12 and 16 weeks were significantly lower than that in normal mice (P0.05). The gas levels of H2S, CBS activity and CBS expression in the hip