心脑血管病防治2023，Vol.23Issue(11)：4-10,7.DOI:10.3969/j.issn.1009-816x.2023.11.002
银杏二萜内酯调控PI3K/Akt/Nrf2通路改善糖尿病脑病大鼠认知功能的机制研究
Mechanism of ginkgo diterpene lactone regulating phosphatidylinositol 3 kinase/protein kinase B/nuclear factor E2 related factor 2 pathway to improve the cognitive function in diabetic encephalopathy rats
摘要
Abstract
Objective To investigate the improvement of cognitive function in diabetic encephalopathy(DE)rats by ginkgo diterpene lactone(GDL),and explore the mechanism based on phosphatidylinositol 3 kinase/protein kinase B/nuclear factor E2 related factor 2(PI3K/Akt/Nrf2)pathway.Methods A DE rat model was established by intraperitoneal injection of 35 mg/kg streptozotocin after 4 weeks of high sugar and high fat diet.Rats were divided into the model group,GDL(2.3 mg/kg)group,LY294002(PI3K inhibitor,3 mg/kg)group and GDL combined with LY294002(2.3 mg/kg GDL plus 3 mg/kg LY294002)group,with 12 rats in each group.A control group was also included.After given drugs by intraperitoneal injection once a day for 14 days,cognitive function was measured by water maze test;levels of fasting blood glucose(FBG)and insulin(INS)were measured;histopathological changes in hippocampal neurons were observed by HE staining;activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and the levels of malondialdehyde(MDA),interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α in the hippocampal tissue were detected;and the expression levels of Akt,p-Akt,Nrf2,p-Nrf2,HO-1,NF-κB p65,and p-NF-κB p65 were detected by Western blot.Results Compared to the model group,the escape latency in GDL group decreased(P<0.05),the number of platform crossings increased(P<0.05);FBG and INS levels decreased(both P<0.05),and histopathological changes in hippocampal neurons were significantly improved;SOD and GSH-Px activities increased(both P<0.05),while MDA,IL-1β,IL-6 and TNF-α levels decreased(all P<0.05);the expression levels of p-Akt,p-Nrf2,HO-1,and the ratios of p-Akt/Akt and p-Nrf2/Nrf2 increased(all P<0.05),the expression level of p-NF-κB p65 and the ratio of p-NF-κB p65/NF-κB p65 decreased(both P<0.05).LY294002 significantly reversed the regulatory effects of GDL on various detection indexes in DE rats.Conclusion GDL can inhibit the inflammation and oxidative stress in hippocampus of DE rats,reduce hippocampal neurons damage,and improve cognitive function.Its mechanism may be related to the promotion of PI3K/Akt/Nrf2 pathway activation.关键词
银杏二萜内酯/糖尿病脑病/认知功能/磷脂酰肌醇3激酶/蛋白激酶B/核因子E2相关因子2通路/血糖Key words
Ginkgo diterpene lactone/Diabetic encephalopathy/Cognitive function/Phosphatidylinositol 3 kinase/protein kinase B/nuclear factor E2 related factor 2 pathway/Blood glucose引用本文复制引用
徐丽丽,高明,王利存,丁澄,赵静,邓坤,杨丽君..银杏二萜内酯调控PI3K/Akt/Nrf2通路改善糖尿病脑病大鼠认知功能的机制研究[J].心脑血管病防治,2023,23(11):4-10,7.基金项目
河北省廊坊市科技支撑计划项目(2020013137) （2020013137）
