基于信号通路的中药保护青光眼视网膜神经节细胞药理机制研究进展  

Progress on the pharmacological mechanism of retinal ganglion cells in glaucoma based on signaling pathway

作　　者：刘稳 赵磊[2] 左韬[2] LIU Wen;ZHAO Lei;ZUO Tao(Liaoning University of Traditional Chinese Medicine,Shenyang 110000,China;不详)

机构地区：[1]辽宁中医药大学研究生院,沈阳110000 [2]辽宁中医药大学附属第二医院眼科

出　　处：《环球中医药》2023年第12期2590-2597,共8页Global Traditional Chinese Medicine

摘　　要：青光眼是不可逆性致盲性眼病,视神经萎缩是其特征性表现,视网膜神经节细胞(retinal ganglion cells,RGCs)的凋亡是青光眼视神经萎缩的病理基础。磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路作为一条促存活通路,广泛参与细胞增殖、分化、凋亡等活动,活络效灵丹等中药可通过靶向PI3K/Akt通路上凋亡信号分子抑制RGCs凋亡,保护视神经。丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路可调节炎症、凋亡、氧化等病理活动,槲皮素等通过抑制该通路激活,减轻RGCs炎症反应及氧化应激等损伤。低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是真核细胞对缺氧反应的起始转录因子,过量的HIF-1会促发凋亡和新生血管产生。疏肝通窍方等可通过抑制HIF-1的表达,提高RGCs存活率。Rho激酶(Rho-associated kinase,ROCK)信号通路参与调节细胞骨架重组,改变小梁细胞结构,影响房水排出。青光安Ⅱ号方等具有抑制ROCK通路活化功能,可降低眼压,延缓青光眼进展。Wnt/β-catenin信号通路是细胞生长、组织重塑和器官形成的重要途径,可导致多种神经退行性疾病发生,中药复方活血方通过下调该通路相关因子可减轻RGCs丢失。本文总结了中药干预青光眼RGCs凋亡的关键基因和信号通路,寻找相关信号通路的靶向激动剂或阻断剂,以期更好指导临床和后续研究。Glaucoma is the first irreversible ophthalmopathy causing blindness in the world.Optic nerve atrophy is its characteristic manifestation.Apoptosis of retinal ganglion cells(RGCs)is the pathological basis of glaucoma optic nerve atrophy.As a survival pathway,PI3K/Akt signal pathway is widely involved in cell proliferation,differentiation,apoptosis and other activities.Traditional Chinese medicine such as Huoluo Xiaoling Dan can inhibit RGCs apoptosis and protect the optic nerve by targeting apoptosis signal molecules on PI3K/Akt pathway.MAPK signal pathway can regulate inflammation,apoptosis,oxidation and other pathological activities.Quercetin can inhibit the activation of this pathway and down-regulate the injury of RGCs inflammation and oxidative stress.HIF-1 is the initial transcription factor of eukaryotic cells in response to hypoxia.Excessive HIF-1 will promote apoptosis and neovascularization.Shugan Tongqiao recipe can improve the survival rate of RGCs by inhibiting the expression of HIF-1.ROCK signal pathway is involved in regulating cytoskeleton reorganization,changing trabecular cell structure and affecting aqueous humor excretion.QingguanganⅡcan inhibit the activation of ROCK pathway,reduce intraocular pressure and delay the progression of glaucoma.Wnt/β-catenin signal pathway is an important pathway of cell growth,tissue remodeling and organogenesis,which can lead to a variety of neurodegenerative diseases.Traditional Chinese medicine compound Huoxue recipe can reduce the loss of RGCs by down-regulating the related factors of this pathway.This paper summarized the key genes and signal pathways of traditional Chinese medicine intervention in glaucoma RGCs apoptosis,looking for targeted agonists or blockers of related signal pathways,in order to guide clinical and follow-up research most preferably.

关 键 词：青光眼 视网膜神经节细胞 中药 信号通路 研究进展 

分 类 号：R285[医药卫生—中药学]