中国药房2024，Vol.35Issue(8)：942-947,6.DOI:10.6039/j.issn.1001-0408.2024.08.08
姜黄素对糖尿病并发抑郁症模型大鼠的改善作用及机制
Ameliorative effect and mechanism of curcumin on diabetes model rats with depression
摘要
Abstract
OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway.METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression.The successfully modeled rats were randomly divided into model group,positive control group(0.18 g/kg metformin and 1.8 mg/kg fluoxetine,gavage),curcumin low-dose and high-dose groups(30,60 mg/kg,gavage)and curcumin high-dose+CREB inhibitor group[60 mg/kg curcumin(gavage)+5 mg/kg CREB inhibitor 666-15(intraperitoneal injection)],with 12 rats in each group.Another 12 healthy rats were selected as the normal group.Each group was given a corresponding intervention for 4 weeks,the fasting blood glucose level of rats was detected,and the depression of rats was assessed.The levels of corticosterone(CORT)and inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6]in serum,and the levels of norepinephrine(NE)and 5-hydroxytryptamine(5-HT)in hippocampal tissue were determined.The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group;the expression levels of CREB,BDNF mRNA and protein in hippocampal tissue were detected.RESULTS Compared with the normal group,the hippocampal tissue of rats in the model group was severely damaged,and neurons were scattered,while the fasting blood glucose,the forced swimming immobility time,the tail suspension immobility time,serum levels of CORT,TNF-α,IL-1β and IL-6,and neuron apoptosis indexes were all increased or prolonged significantly(P＜0.05).The levels of NE and 5-HT,the number of surviving neurons,and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly(P＜0.05).Compared with the model group,the damage to hippocampal tissue was relieved in the positive control group and curcumin groups,while the above indexes were improved significantly(P＜0.05).The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group(P＜0.05).CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats(P＜0.05).CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression,and relieve neuronal damage and inflammatory response,the mechanism of which may be associated with activating CREB/BDNF signaling pathway.关键词
姜黄素/糖尿病/抑郁症/CREB/BDNF信号通路/炎症反应/海马组织/神经元Key words
curcumin/diabetes/depression/CREB/BDNF signaling pathway/inflammation reaction/hippocampal tissue/neurons分类
医药卫生引用本文复制引用
张洪艳,张玉平,张燕娇,郑静静,卞睿,李文慧,任卫东..姜黄素对糖尿病并发抑郁症模型大鼠的改善作用及机制[J].中国药房,2024,35(8):942-947,6.基金项目
河北省医学科学研究课题计划项目(No.20200529) （No.20200529）
河北省中医药类科研计划项目(No.2021189) （No.2021189）
