
科学技术与工程

中国技术经济学会
七味白术散对糖尿病认知功能障碍大鼠海马Wnt/β-catenin信号通路的影响
高佳馨 , 李阳 , 薛亚楠 , 张云雨 , 冯晓帆
科学技术与工程 ›› 2025, Vol. 25 ›› Issue (34) :14576-14582
七味白术散对糖尿病认知功能障碍大鼠海马Wnt/β-catenin信号通路的影响
Qiwei Baizhu Powder on Hippocampus of Diabetic Rats with Cognitive Dysfunction Effect of Wnt/β-catenin Signaling Pathway
以长期高脂饲料喂养联合1%链脲佐菌素建立筛选出的糖尿病认知功能障碍(diabetic cognitive impairment, DCI)大鼠模型为实验材料,观察七味白术散对大鼠海马内Wnt/β-连环蛋白(β-catenin)信号途径的影响。DCI大鼠成模后,分别设对照(DZ)组、模型(MX)组、七味白术散(QWBZ)组、联合西药(二甲双胍·罗格列酮,LHXY)组。各组给予相应药物(七味白术散1.6 g/mL,联合西药52 mg/mL)及生理盐水灌胃6周(2 mL/只)后,取眶静脉血检测大鼠空腹血糖(fasting plasma glucose, FPG),空腹胰岛素(fasting insulin, FINS)水平,得出胰岛素敏感指数(insulin sensitivity index, ISI);采用Morris水迷宫(Morris water maze, MWM)系统评估DCI大鼠空间寻找路径及用时的变化;HE染色切片观察大鼠海马形态病理变化;qPCR法和Western blot法分别检测海马组织内腺瘤性息肉病(adenomatous polyposis coli, APC)、β-catenin、糖原合成酶激酶3β(GSK-3β)mRNA及蛋白表达情况;IHC法检测磷酸化(p)-GSK-3β蛋白表达分布水平。结果显示,七味白术散能够有效降低DCI大鼠FPG(P<0.01),调节ISI指数(P<0.01),改善海马组织神经细胞形态破坏;与MX组相比,七味白术散能够明显降低大鼠海马组织内APC、GSK-3β mRNA和蛋白表达(P<0.01),提高β-catenin表达(P<0.01),使p-GSK-3β蛋白相对表达升高(P<0.01),以缓解海马神经元损伤。七味白术散可能通过调节Wnt/β-catenin信号通路,发挥对糖尿病所并发认知功能障碍的干预作用。
To investigate the impact of Qiwei Baizhu Powder on the Wnt/β-catenin signaling pathway in the hippocampus of DCI(diabetic cognitive impairment) rat model established through prolonged high-fat diet feeding combined with 1% streptozotocin administration. Following successful establishment of the DCI model, five groups were designated: DZ(control) group, MX(model) group, QWBZ (Qiwei Baizhu powder) group, and a combination Western medicine group (metformin and rosiglitazone, LHXY). After each group received the respective treatments of QWBZ (1.6 g/mL) in combination with Western medicine (52 mg/mL) or normal saline for a period of 6 weeks (2 mL per animal), orbital venous blood was collected to measure FPG (fasting plasma glucose) levels. FINS(fasting insulin) levels were determined using ELISA, and ISI (insulin sensitivity index) was subsequently calculated. MWM (Morris water maze) system was utilized to assess the alterations in spatial navigation paths and times of rats subjected to DCI(delayed cerebral ischemia). The morphological changes in rat hippocampal tissue were obtained through HE (hematoxylin and eosin)-stained sections. The mRNA and protein expression levels of PKA (protein kinase A), β-catenin, and GSK-3β (glycogen synthase kinase 3β) were quantified by qPCR (quantitative real-time PCR) and Western blot analysis, respectively. IHC (immunohistochemistry) was employed to investigate the expression and distribution of phosphorylated GSK-3β protein. The results show that Qiwei Baizhu Powder can effectively reduce the FPG value of DCI rats (P<0.01), regulate ISI index (P<0.01), and improve the morphological destruction of nerve cells in hippocampus. Compared with MX group, Qiwei Baizhu Powder could significantly reduce the expression of APC and GSK-3β mRNA and protein in hippocampus of rats (P<0.01), increase the expression of β-catenin (P<0.01), and increase the relative expression of P-GSK-3β protein (P<0.01), so as to alleviate the damage of hippocampal neurons. Qiwei Baizhu Powder may play a role in the intervention of cognitive dysfunction complicated by diabetes mellitus by regulating Wnt/β-catenin signaling pathway.
糖尿病认知功能障碍 / 七味白术散 / Wnt/β-catenin信号通路 / GSK-3β
diabetic cognitive dysfunction / Qiwei Baizhu Powder / Wnt/β-catenin signaling pathway / GSK-3β
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