毛蕊花糖苷调节ERK1/2-CREB-BDNF信号通路改善糖尿病大鼠的认知障碍OA
Acteoside ameliorates cognitive impairment in diabetic rats by modulating the ERK1/2-CREB-BDNF signaling pathway
目的 探讨毛蕊花糖苷(acteoside,ACT)对糖尿病大鼠认知障碍的改善作用及调节ERK1/2-CREB-BDNF信号通路的作用.方法 SD大鼠随机分为正常组、模型组、多奈哌齐组、二甲双胍组及ACT低、中、高剂量组,每组15只.采用高脂高糖饲料联合链脲佐菌素(STZ)注射建立糖尿病大鼠模型.检测给药前后各组大鼠空腹血糖;Morris水迷宫评估空间学习记忆;HE染色观察海马病理;ELISA检测皮层炎症因子及β淀粉样蛋白含量;Western blot检测海马ERK1/2、p-ERK1/2、CREB、p-CREB、BDNF、TrkB蛋白表达.结果 与正常组相比,模型组大鼠水迷宫逃避潜伏期延长、站台时间减少,海马CA1、CA3区神经细胞明显损伤,血糖、皮层炎症因子及Aβ含量、海马p-ERK1/2/ERK1/2比值明显升高(P<0.05),海马p-CREB/CREB比值及BDNF、TrkB表达水平明显降低(P<0.05).与模型组相比,ACT各组及二甲双胍组空腹血糖明显降低(P<0.05),ACT各组及多奈哌齐组明显缩短逃避潜伏期、延长站台时间,并升高海马p-CREB/CREB蛋白表达比值(P<0.05);ACT各组、多奈哌齐组及二甲双胍组明显降低皮层炎症因子及Aβ含量、降低海马p-ERK1/2/ERK1/2比值(P<0.05);ACT各组海马BDNF、TrkB表达明显升高(P<0.01);各给药组海马神经细胞病理损伤明显改善.结论 ACT可能通过调节ERK1/2-CREB-BDNF信号通路,抑制炎症因子含量、Aβ沉积及空腹血糖含量,改善糖尿病大鼠的认知障碍,发挥神经保护作用.
Aim To investigate the improvement ef-fect of acteoside(ACT)on cognitive impairment in diabetic rats and its regulatory role in the ERK1/2-CREB-BDNF signaling pathway.Methods Sprague-Dawley(SD)rats were randomly divided into the fol-lowing groups(15 rats per group):normal control group,model group,donepezil group,metformin group,and low-,medium-,and high-dose ACT groups.Diabetic rat models were established by feed-ing a high-fat/high-sucrose diet combined with strepto-zotocin(STZ)injection.Fasting blood glucose levels were measured before and after drug administration.Spatial learning and memory were assessed using the Morris water maze test.Hippocampal pathology was observed via hematoxylin-eosin(HE)staining.Corti-cal inflammatory factors and β-amyloid content were detected by ELISA.Hippocampal expression levels of ERK1/2,p-ERK1/2,CREB,p-CREB,BDNF,and TrkB proteins were analyzed by Western blotting.Re-sults Compared with the normal group,the model group exhibited significantly prolonged escape latency and reduced platform time in the water maze test,se-vere neuronal damage in hippocampal CA1 and CA3 regions,elevated fasting blood glucose,increased cor-tical inflammatory factors and Aβ content,and el-evated hippocampal p-ERK1/2 to ERK1/2 ratio(P<0.05),while showing reduced hippocampal p-CREB to CREB ratio and decreased BDNF and TrkB expres-sion levels(P<0.05).Compared with the model group,both ACT-treated groups and the metformin group demonstrated significantly reduced fasting blood glucose(P<0.05).ACT-treated groups and the done-pezil group showed significantly shortened escape la-tency,prolonged platform time,and increased hippo-campal p-CREB/CREB ratio(P<0.05).ACT-treated groups,donepezil group,and metformin group exhib-ited reduced cortical inflammatory factors and Aβ con-tent,and decreased hippocampal p-ERK1/2 to ERK1/2 ratio(P<0.05).ACT-treated groups specifically dis-played significantly elevated hippocampal BDNF and TrkB expression(P<0.01).All drug-administered groups showed marked improvement in hippocampal neuronal pathology.Conclusion ACT may exert neu-roprotective effects by modulating the ERK1/2-CREB-BDNF signaling pathway,suppressing inflammatory factors,reducing Aβ deposition,and lowering fasting blood glucose levels,thereby ameliorating cognitive impairment in diabetic rats.
马玉彩;吕英爽;黄秀环;李建梅;闫明;高莉
新疆医科大学药学院,新疆 乌鲁木齐 830017新疆医科大学药学院,新疆 乌鲁木齐 830017新疆医科大学药学院,新疆 乌鲁木齐 830017新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830011新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830011新疆维吾尔自治区药物研究院,新疆 乌鲁木齐 830011
医药卫生
毛蕊花糖苷糖尿病认知障碍神经保护炎症ERK1/2-CREB-BDNF信号通路
acteosidediabetes mellituscognitive impairmentneuroprotectioninflammationERK1/2-CREB-BDNF signaling pathway
《中国药理学通报》 2026 (4)
660-666,7
新疆维吾尔自治区自然科学基金重点项目(No 2022D01D25)新疆维吾尔自治区重点研发计划项目(No 2022B02047)
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