Z-十八碳-9-烯-丙磺酰胺对糖尿病认知功能障碍小鼠学习记忆功能的影响  

Effects of Z-9-octadecenyl-2-propanesulfonamide on the learning and memory function of diabetes-associated cognitive decline

作　　者：王翠宝 李莹 卢华辉 魏南服 黄硕 王韵 饶荣 许淑珍 任桐[3] WANG Cui-bao;LI Ylng;LU Hua-hui;WEI Nan-fu;HUANG Shuo;WANG Yun;RAO Rong;XU Shu-zhen;REN Tong(Department of Anesthesiology,Xiamen Fifth Hospital,Xiamen 361000,China;Department of Pharmacy,Xiamen Medical College,Xiamen 361023,China;Medical College,Xiamen University,Xiamen 361105,China)

机构地区：[1]厦门市第五医院麻醉科,福建厦门361000 [2]厦门医学院药学系,福建厦门361023 [3]厦门大学医学院,福建厦门361105

出　　处：《药学学报》2018年第9期1504-1510,共7页Acta Pharmaceutica Sinica

基　　金：福建省教育厅资助项目(JAT160583)

摘　　要：探索新化合物Z-十八碳-9-烯-丙磺酰胺(N15)对糖尿病认知功能障碍(DACD)小鼠学习记忆功能的作用及机制。采用链脲佐菌素(STZ)连续小剂量腹腔注射以及高脂高糖加STZ诱导2型糖尿病小鼠模型,N15(50和100mg·kg^(-1)·d^(-1))连续灌胃给药6周,于给药末期进行跳台、避暗以及Morris水迷宫测试以评价小鼠学习记忆功能;对海马内葡萄糖和乳酸水平进行测定;通过realtimePCR测定海马内突触成长相关蛋白-43(GAP-43)、突触素(SYN)、脑源性生长因子(BDNF)和神经营养因子-3(NT-3)m RNA的表达。结果表明,N15可显著改善模型小鼠学习记忆能力,降低海马内葡萄糖和乳酸含量,显著上调海马内GAP-43、SYN、BDNF和NT-3 m RNA表达水平。上述结果表明,新型化合物N15具有改善糖尿病认知功能障碍的作用,其机制可能与增加海马内突触生长相关因子和神经营养因子表达相关。This study was designed to investigate the therapeutic effect of novel compound Z-9-octadecenyl-2-propanesulfonamide（N15） on diabetes-associated cognitive decline（DACD）. Type 2 diabetes（T2 DM） mice models were established with multiple injection of low doses of streptozotocin（STZ） in mice on high fat diet（HFD）. Vehicle and different concentrations of N15（50 and 100 mg·kg^（-1）·d^（-1）） were administrated orally for 6 weeks. The step-down test, dark avoidance task and Morris water maze were conducted at the 6 th week. The level of glucose and lactic acid in hippocampus were determined and m RNA of growth associated protein-43（GAP-43）, synaptophysin（SYN）, brain derived neurotrophic factor（BDNF） and neurotrophins-3（NT-3） in hippocampus were analyzed by real time PCR. The beneficial effects of N15 on learning and memory were found in the test of step-down, dark avoidance and Morris water maze. N15 reduced the level of glucose and lactic acid in hippocampus of HFD＋STZ-induced diabetic encephalopathy model mice. Additionally, the m RNA expression of GAP-43, SYN, BDNF and NT-3 in hippocampus of HFD＋STZ-induced diabetic encephalopathy mice were significantly increased by N15（P〈0.01）. These results suggest that the novel compound N15 can ameliorate diabetes-associated cognitive decline and the potential mechanism may be associated with the expressions of increased synaptic-related factors and neurotrophic factor in the hippocampus of diabetes-associated cognitive decline in mice.

关 键 词：Z-十八碳-9-烯-丙磺酰胺 糖尿病认知功能障碍 海马 神经保护 

分 类 号：R964[医药卫生—药理学]