首页|温肺降浊方通过调节Nrf2/Keap 1-GPx4信号通路抑制铁死亡改善血管性痴呆模型大鼠认知功能障碍的研究

温肺降浊方通过调节Nrf2/Keap 1-GPx4信号通路抑制铁死亡改善血管性痴呆模型大鼠认知功能障碍的研究

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目的:观察温肺降浊方对血管性痴呆模型大鼠的影响，探究其可能的作用机制。方法:制备永久性双侧颈总动脉闭塞(2VO)大鼠模型，使用Ferrostatin-1抑制剂和温肺降浊方2。95、5。9、11。8 g/kg干预，持续2个月。观察成模后大鼠学习认知能力，HE染色观察海马病理情况，普鲁士蓝染色、免疫组化、qRT-PCR和Western Blot法检测大鼠海马组织中铁沉积和GPx4、Nrf2、HO-1、Keap 1、Cox2 mRNA及蛋白的表达情况。结果:与假手术对照组比较，模型对照组大鼠逃避潜伏期延长、穿越平台次数明显缩短(P<0。05)，海马细胞出现明显水肿及棕蓝色铁颗粒沉积;海马组织中GPx4、Nrf2、HO-1蛋白及mRNA的表达下调(P<0。05)，Keap 1、Cox2蛋白及mRNA的表达上调(P<0。05);与模型对照组比较，Ferrostatin-1抑制剂和温肺降浊方各剂量组大鼠逃避潜伏期缩短、穿越平台次数明显增加(P<0。05)，海马组织细胞水肿化减少;GPx4、Nrf2、HO-1蛋白及mRNA的表达上调(P<0。05)，Keap 1、Cox2蛋白及mRNA的表达下调(P<0。05)。结论:温肺降浊方可能通过调节Nrf2/Keap 1/GPx4信号通路相关蛋白抑制铁死亡，从而减少大脑海马组织中铁颗粒的沉积，从而改善大脑认知情况，以温肺降浊方11。8 g/kg组作用最佳。
Wenfei Jiangzhuo (温肺降浊) Formula Inhibits Ferroptosis by RegulatingNrf2/Keap 1-GPx4 Signaling Pathway to Treat Cognitive Impairment in the Rat Model of Vascular Dementia
Objective:To observe the effect of Wenfei Jiangzhuo (温肺降浊) Formula on vascular dementia in rats and decipher the possible mech-anism.Methods:The rat model of 2-vessel occlusion was established and then treated with ferrostatin-1 inhibitor and Wenfei Jiangzhuo For-mula at 2.95,5.9,and 11.8 g/kg for 2 months.The cognitive learning ability of the rats was observed after modeling.Hematoxylin-eosin staining and Prussian blue staining were employed to detect the iron deposition in the hippocampus.Immunohistochemistry,qRT-PCR,and Western blotting were employed to determine the expression of glutathione peroxidase 4 (GPx4),nuclear factor-erythroid 2 related factor 2 (Nrf2),heme oxygenase 1 (HO-1),Kelch-like ECH-associated protein 1 (Keap 1),and cyclooxygenase-2 (Cox2) in the hippocampus.Re-sults:Compared with the sham group,the model group showed prolonged escape latency and reduced platform crossings (P<0.05),obvious e-dema and deposition of brown-blue iron particles in the hippocampus cells,down-regulated expression of GPx4,Nrf2,and HO-1 (P<0.05),and up-regulated expression of Keap 1 and Cox2 (P<0.05) in the hippocampus.Compared with the model group,the ferrostatin-1 inhibitor and Wenfei Jiangzhuo Formula shortened the escape latency and increased the platform crossings (P<0.05),reduced the edema in the hippo-campus,up-regulated the expression of GPx4,Nrf2,and HO-1 (P<0.05),and down-regulated the expression of Keap 1 and Cox2 (P<0.05).Conclusion:Wenfei Jiangzhuo Formula may inhibit ferroptosis by regulating the expression of proteins associated with the Nrf2/Keap 1-GPx4 signaling pathway to reduce the deposition of iron particles in the hippocampus,thus improving the cognitive condition of the brain.Wenfei Jiangzhuo Formula administrated at 11.8 g/kg demonstrated the best effect.

Wenfei Jiangzhuo (温肺降浊) FormulaNuclear factor-erythroid 2 related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap 1)-glutathione peroxidase 4 (GPx4) signaling pathwayFerroptosisVascular dementiaCognitive impairment

张鼎、李方存、姜明贺、周珂青、秦红玲、陈炜、胡跃强

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广西中医药大学,南宁 530001

广西中医药大学第一附属医院,南宁 530023

温肺降浊方 核因子-红细胞2相关因子2/Kelch样ECH关联蛋白1/谷胱甘肽过氧化物酶4信号通路 铁死亡 血管性痴呆 认知功能障碍

2024

中药药理与临床
中国药理学会 四川省中医药科学院

中药药理与临床

北大核心
影响因子：0.996
ISSN：1001-859X
年,卷(期)：2024.40(10)