[1]沈兆星,肖谦,赵宇星,等.Ghrelin对糖尿病大鼠海马DKK-1表达和学习记忆功能的影响[J].南方医科大学学报,2016,(04):500.
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Ghrelin对糖尿病大鼠海马DKK-1表达和学习记忆功能的影响()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2016年04期
页码:
500
栏目:
出版日期:
2016-04-16

文章信息/Info

Title:
Effects of ghrelin on hippocampal DKK-1 expression and cognitive function in rats with diabetes mellitus
作者:
沈兆星肖谦赵宇星赵柯湘
关键词:
Ghrelin糖尿病认知功能DKK-1β-catenin
Keywords:
ghrelin diabetic cognitive function DKK-1 β-catenin
摘要:
目的观察Ghrelin对糖尿病大鼠DKK-1和WNT信号通路的表达变化,探讨其参与学习记忆功能的机制。方法60只SD 大鼠随机均分为对照组(NC组)、糖尿病组(DM组)、糖尿病+Ghrelin 组(DM1 组)、糖尿病+Ghrelin+D-lys3-GHRP-6 组(DM2 组)。腹腔注射STZ(60 mg/kg)建立糖尿病大鼠模型,Morris水迷宫实验检测大鼠空间学习和记忆能力;电镜观察大鼠海马CA1 区超微结构,普通显微镜下HE染色观察大鼠海马CA1 区细胞形态;ELISA 检测大鼠血清DKK-1 的表达;荧光定量PCR及 Western blotting分别检测大鼠海马DKK-1及β-catenin mRNA和蛋白水平。结果与NC组相比,DM组大鼠逃避潜伏期延长, 穿越平台次数减少(P<0.05);神经元细胞肿胀、线粒体空泡变性等(P<0.05);神经元细胞排列紊乱,细胞核固缩等;血清、海马组 织中DKK-1的表达明显升高(P<0.05),海马中β-catenin表达下降(P<0.05)。与DM组相比,DM1组大鼠逃避潜伏期缩短,穿越 平台次数增多(P<0.05);神经元细胞形态完整,线粒体发达、密度增加等(P<0.05);神经元细胞排列整齐、细胞层数清晰;血清、 海马组织中DKK-1表达明显降低(P<0.05),海马中β-catenin的表达升高(P<0.05)。联合应用Ghrelin和GHSR-1a受体拮抗剂 Ghrelin+D-lys3-GHRP-6 后,Ghrelin 上述作用被阻断(P<0.05)。结论WNT信号通路可能参与糖尿病脑病的发生发展过程, Ghrelin改善糖尿病大鼠学习记忆功能的机制至少部分与下调海马DKK-1的表达、调控WNT信号通路有关。
Abstract:
Objective To explore the effects of ghrelin on learning and memory abilities and expressions of DKK-1 and β-catenin in the hippocampus of diabetic rats. Methods Sixty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, ghrelin-treated diabetic group (DM1 group), and ghrelin- and D-lys3-GHRP-6 (a GHSR-1a receptor antagonist)-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (65 mg/kg). The learning and memory abilities of the rats were assessed with Morris water maze (MWM) test. The ultrastructure of the hippocampal CA1 area of the rats were observed with electron microscopy. Serum levels of DKK-1 were examined by ELISA, and the expressions of DKK-1 and β-catenin in the hippocampus were examined by quantitative real-time PCR and Western blotting. Results Compared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05), increased expression of DKK-1 and lowered β-catenin expression in the hippocampus (P<0.05), significant ultrastructural injuries and disordered arrangement of neurons with the nuclear pycnosis in the hippocampal CA1 area. Ghrelin treatment of the diabetic rats obviously improved their learning and memory abilities (P<0.05), reduced DKK-1 and increased β-catenin expressions (P<0.05), ameliorated ultrastructural damages in the hippocampal CA1 area and restored normal neuronal alignment with clear cell layers. Such effects of ghrelin were antagonized by treatment with D-lys3-GHRP-6 in the diabetic rats. Conclusion Ghrelin can alleviate learning and memory dysfunction in diabetic rats possibly by down-regulating the expressions of DKK-1 and activating the WNT signaling pathways.

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更新日期/Last Update: 1900-01-01