2型糖尿病大鼠认知行为的改变及新型褪黑素受体激动剂Neu-P11的调节作用  

Changes of Cognitive Function Type 2 Diabetes Mellitus Rats and Regulated Effect of New Melatonin Receptor Agonist Neu-P11

作　　者：周珺[1,2] 张锦[1] 刘悦[1] 李茂星[1,2] 岳颖[1,2] 张汝学[1,2] 贾正平[1,2] 

机构地区：[1]兰州军区兰州总医院全军高原环境损伤防治重点实验室,兰州730050 [2]兰州大学药学院,兰州730000

出　　处：《解放军医药杂志》2017年第6期6-9,共4页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金资助项目(30772773、81173620)

摘　　要：目的评价2型糖尿病大鼠认知功能的变化和新型褪黑素受体激动剂Neu-P11的调节作用及其作用机制。方法采用高脂饲料喂养2月联合腹腔注射链脲佐菌素(STZ)建立2型糖尿病大鼠模型,分为正常对照组、模型组和Neu-P11组,各8只;正常对照组和模型组每日1次灌胃生理盐水,Neu-P11组每日1次灌胃Neu-P11(5 mg/kg)。第25天进行情绪唤醒实验,第32天进行旷场实验,第34天收集24 h尿液测定尿游离肾上腺皮质激素(CORT)水平,第35天断头处死大鼠并收集躯干血测定血清促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和CORT水平。结果模型组情绪唤醒实验综合得分低于正常对照组(P<0.05),而Neu-P11组与模型组比较差异无统计学意义(P>0.05)。模型组中央格停留时间长于对照组(P<0.05),水平运动得分和垂直运动得分低于正常对照组(P<0.01);Neu-p11组中央格停留时间短于模型组(P<0.05),垂直运动得分高于模型组(P<0.05)。模型组尿CORT水平显著高于正常对照组(P<0.01)。Neu-P11组血清CRH、CORT及尿CORT水平低于模型组(P<0.05,P<0.01),而血清ACTH水平高于模型组(P<0.05)。结论新型褪黑素受体激动剂Neu-P11可改善2型糖尿病大鼠的认知功能障碍,降低下丘脑-垂体-肾上腺轴功能亢进可能是其主要的作用机制。Objective To evaluate changes of cognitive function in type 2 diabetes mellitus （T2DM） rats and regulated effect of new melatonin receptor agonist Neu-Pll and its mechanism of action. Methods T2DM rat models were established by high fat diet for 2 months combined with Streptozotocin （STZ） by intraperitoneal injection, and the rats were divided into control group, model group and Neu-P11 group （n = 8 for each group）. Control and model groups were lavaged with normal saline （1 time/d） , while Neu-Pll group was lavaged with Neu-Pll （5 mg/kg, 1 time/d）. E- motional awaken test was performed at 25Lh d after treatment; open field test was performed at 32th d after treatment; urine within 24h was collected at 34＂ d after treatment to detect urinary freeing corticosterone （CORT） level; all rats were sac- rificed by decapitation at 35th d after treatment and trunk blood was collected to detect plasma corticotropin release hormone （CRH） , adrerrmrticotropic hormone （ACTH） and CORT levels. Results In model group, score of emotional a- waken test was significantly lower than that in control group （P 〈 0. 05） , but there was no significant difference in the score between Neu-P11 and model groups （P 〉 0. 05）. Compared with those in control group, in model group, residence time in central zone was longer （ P 〈 0.05 ）, while scores of horizontal movement and vertical movement were significantly lower （ P 〈 0. 01 ）. In Neu-pl 1 group, residence time in central zone was shorter （ P 〈 0.05 ） , while vertical movement score was significantly higher than those in model group （ P 〈 0.05）. Urinary CORT level in model group was significantly higher than that in control group （P 〈0. 01）. In Neu-Pll group, serum CRH, CORT and urinary CORT levels were significantly lower （P 〈 0.01, P 〈 0.05 ） , while serum ACTH level was significantly higher than those in model group （P 〈0, 05）. Conclusion New melatonin receptor agonist Neu-Pll may improve cognitive d

关 键 词：糖尿病 2型 认知障碍 褪黑激素 Neu-P11 大鼠 Wistar 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]