沙格列汀对糖尿病并发抑郁症大鼠认知功能的影响  

Effects of saxagliptin on cognitive function in rats with diabetes mellitus complicated with depression

作　　者：盛飞[1] 李庭毅[1] 李文辉[1] Sheng Fei;Li Tingyi;Li Wenhui(Department of Neurology,the Central Hospital of Xiaogan,Xiaogan 432000,China)

机构地区：[1]湖北省孝感市中心医院神经内科,432000

出　　处：《神经疾病与精神卫生》2020年第10期717-721,F0003,共6页Journal of Neuroscience and Mental Health

摘　　要：目的探讨二肽基肽酶-Ⅳ(DPP-4)抑制剂沙格列汀对糖尿病并发抑郁症(DD)大鼠认知功能的影响,以及可能的机制。方法48只无特定病原体级健康雄性SD大鼠随机分为对照组、模型组、阳性药组和沙格列汀组,每组12只。采用高脂乳剂灌胃14 d+经尾静脉注射链脲佐菌素(STZ)+28 d慢性刺激制备DD模型,在接受慢性刺激的同时,阳性药组大鼠给予二甲双胍+氟西汀胶囊灌胃,沙格列汀组大鼠给予沙格列汀灌胃,模型组和对照组则给予等量的生理盐水,每天1次,连续28 d。旷场实验和Morris水迷宫实验检测大鼠对周围陌生环境探索能力和学习记忆能力,苏木素-伊红染色观察大鼠海马组织形态变化,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色检测海马组织中神经细胞凋亡,酶联免疫吸附试验检测海马组织中IL-1β、IL-6和TNF-α水平。结果与对照组比较,模型组、阳性药组和沙格列汀组大鼠水平穿越格数[(62.25±5.53)、(85.92±4.58)、(78.25±6.02)个比(104.75±6.11)个]和直立次数[(7.33±1.97)、(11.17±1.34)、(9.33±2.27)次比(17.50±1.68)次]均减少(均P<0.01),逃避潜伏期延长[(51.75±8.01)、(29.58±5.14)、(35.42±3.48)s比(18.17±3.43)s;均P<0.01],而目标象限记忆时间缩短[(15.00±3.52)、(26.08±5.88)、(21.25±4.35)s比(34.42±5.28)s;均P<0.01],大鼠海马组织中神经细胞凋亡指数[(74.66±4.62)%、(47.23±6.24)%和(39.22±2.80)%比(9.22±0.87)%]升高(均P<0.01),IL-1β[(41.26±5.82)、(21.01±3.84)、(29.89±7.42)ng/g比(12.22±5.02)ng/g]、IL-6[(80.792±3.59)、(50.73±7.18)、(61.69±6.29)ng/g比(31.90±4.79)ng/g]和TNF-α[(90.94±8.72)、(66.57±9.93)、(77.70±6.96)ng/g比(49.88±5.24)ng/g]水平升高(P<0.05或P<0.01);与模型组比较,阳性药组和沙格列汀组大鼠水平穿越格数和直立次数均升高(均P<0.01),逃避潜伏期缩短(均P<0.01),而目标象限记忆时间延长(均P<0.01),大鼠海马组织中神经细胞凋亡指数降低(�Objective To investigate of effects of dipeptidyl peptidase-Ⅳ(DPP-4)inhibitor saxagliptin on cognitive function in rats with diabetes mellitus complicated with depression(DD),and possible mechanisms.Methods A total of 48 specific pathogen free(SPF)healthy male SD rats were randomly divided into control group,model group,positive drug group and saxagliptin group,with 12 rats in each group.DD model was established by high-fat emulsion by gavage for 14 days,tail vein injection of streptozotocin(STZ),and chronic stress for 28 days.In the same period of chronic stress,the rats in the positive drug group were given metformin and fluoxetine capsules by gavage,in the saxagliptin group were given saxagliptin by gavage,and in the model group and the control group were given the same amount of normal saline,once a day for 28 days.The open field experiment and the Morris water maze test were used to detect the ability of exploring the unfamiliar environment and the ability of learning and memory.Morphological changes of hippocampus in rats were observed by hematoxylin-eosin(HE)staining.The neuronal apoptosis of hippocampus was detected by TdT mediated dUTP nick end labeling(TUNEL)staining.The levels of IL-1β,IL-6 and TNF-αin hippocampus tissues were detected by enzyme-linked immunosorbent assay(ELISA).Rusults Compared with the control group,the number of horizontal crossing grids of the rats in the model group,in the positive drug group and in the saxagliptin group[(62.25±5.53),(85.92±4.58)and(78.25±6.02)vs.(104.75±6.11)],and the number of standing vertically[(7.33±1.97),(11.17±1.34)and(9.33±2.27)vs.(17.50±1.68)]were decreased(all P<0.05).The escape latency was prolonged[(51.75±8.01)s,(29.58±5.14)s and(35.42±3.48)s vs.(18.17±3.43)s;all P<0.01],while the target quadrant memory time was shortened[(51.75±8.01)s,(29.58±5.14)s and(35.42±3.48)s vs(.18.17±3.43)s;all P<0.01].The neuronal apoptosis index in hippocampus tissues were increased[(74.66±4.62)%,(47.23±6.24)%and(39.22±2.80)%vs.(9.22±0.87)%;all P<0.01

关 键 词：糖尿病 抑郁症 沙格列汀 海马 认知功能 

分 类 号：R587.2[医药卫生—内分泌] R749.4[医药卫生—内科学]