摘要
目的基于环磷酸腺苷反应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路,研究姜黄素对糖尿病并发抑郁症模型大鼠的改善作用及潜在机制。方法采用高脂高糖饲料喂养+腹腔注射链脲佐菌素+慢性不可预测性应激致郁的方法构建糖尿病并发抑郁症模型大鼠。将造模成功的大鼠随机分成模型组,阳性对照组(0.18g/kg二甲双胍和1.8mg/kg氟西汀,灌胃),姜黄素低、高剂量组(30、60mg/kg,灌胃)和姜黄素高剂量+CREB抑制剂组[60mg/kg姜黄素(灌胃)+5mg/kgCREB抑制剂666-15(腹腔注射)],每组12只。另选取12只健康大鼠作为正常组。各组大鼠给予相应干预4周后,检测大鼠空腹血糖并对其抑郁症状进行评估;检测大鼠血清中皮质酮(CORT)、炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6]水平和海马组织中去甲肾上腺素(NE)、5-羟色胺(5-HT)水平;观察大鼠海马组织病理学变化并检测神经元凋亡情况;检测大鼠海马组织中CREB、BDNFmRNA及蛋白的表达水平。结果与正常组相比,模型组大鼠海马组织损伤严重,神经元分散;空腹血糖,强迫游泳不动时间和悬尾不动时间,血清中CORT、TNF-α、IL-1β和IL-6水平,神经元凋亡指数均显著升高或延长(P<0.05);海马组织中NE、5-HT水平,存活神经元数以及CREB、BDNFmRNA及蛋白表达水平均显著降低或减少(P<0.05)。与模型组相比,阳性对照组和姜黄素各剂量组大鼠海马组织损伤有所减轻,各定量指标均显著改善(P<0.05),且姜黄素高剂量组的改善效果显著优于低剂量组(P<0.05);CREB抑制剂可显著逆转高剂量姜黄素对模型大鼠的改善作用(P<0.05)。结论姜黄素可改善糖尿病并发抑郁症模型大鼠的抑郁症状,减轻神经元损伤和炎症反应,其作用可能与激活CREB/BDNF信号通路有关。
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-1βand 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 posi
作者
张洪艳
张玉平
张燕娇
郑静静
卞睿
李文慧
任卫东
ZHANG Hongyan;ZHANG Yuping;ZHANG Yanjiao;ZHENG Jingjing;BIAN Rui;LI Wenhui;REN Weidong(Dept.of Third Neurology,the First Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075000,China;Dept.of Pathophysiology,Hebei North University,Hebei Zhangjiakou 075000,China;Dept.of Cardiovascular Medicine,the Second Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075100,China;Dept.of Endocrinology,the First Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075000,China)
出处
《中国药房》
CAS
北大核心
2024年第8期942-947,共6页
China Pharmacy
基金
河北省医学科学研究课题计划项目(No.20200529)
河北省中医药类科研计划项目(No.2021189)。
