组胺对星形胶质细胞Egr-1表达的调节作用

目的:探讨组胺对星形胶质细胞早期反应生长因子-1(Egr-1)表达是否具有调节作用。方法:将野生型(WT)和组氨酸脱羧酶敲除(HDC-KO)小鼠及组胺处理的HDC-KO小鼠取脑,并提取皮层组织总RNA。将原代培养的大鼠皮层星形胶质细胞分别给予不同浓度的组胺(10^(-8)、10^(-7)、10^(-6)、10^(-5)或10^(-4)mol/L)处理15、30、60、120或240 min。组胺H_1、H_2受体拮抗剂分别于组胺给药前15 min加入。组胺处理完毕后,提取细胞总RNA或蛋白。利用real-time PCR和Western blot测定Egr-1的表达。结果:与WT小鼠相比,HDC-KO小鼠大脑皮层Egr-1的mRNA表达量显著降低,而外源性给予组胺则能促进其Egr-1的mRNA表达。在培养的星形胶质细胞上,组胺可促进Egr-1的mRNA表达,其中10-5mol/L的组胺作用最强,而组胺(10^(-5)mol/L)处理30 min时Egr-1的mRNA表达量达到峰值,相应的Egr-1蛋白表达于60 min时显著增高,该作用可被组胺H_1受体拮抗剂而非H_2受体拮抗剂显著抑制。结论:组胺对大脑皮层组织及培养的星形胶质细胞Egr-1表达具有上调作用,该作用与激动组胺H_1受体有关。

Involvement of MAPK/ERK kinase-ERK pathway in exogenous bFGF-induced Egr-1 binding activity enhancement in anoxia-reoxygenation injured astrocytes

Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.

EGR-1在肝损伤中的作用

肝损伤是多因素引起的复杂病理生理变化,早期生长转录因子-1(EGR-1)在肝损伤中的利弊作用目前仍存在争议.相关研究证实在半乳糖胺/脂多糖诱导的急性肝损伤和异硫氰酸酯(ANIT)诱导的肝内胆汁淤积症小鼠模型中以及机体非肝脏系统的损伤中,EGR-1能够不断加剧肝细胞炎症,促进凋亡.然而,另有一些研究发现EGR-1可以通过调节TNF-α、iNOS、COX-2、NF-κBp65等因子,在CCl4所致肝损伤中起到保护作用.本文就EGR-1在肝损伤中调节的双向作用及其机制进行简要概述.

中药治疗胆汁淤积性肝病作用机制的研究进展

胆汁淤积性肝病具有临床发病率高、病因复杂、发病机制不明确的特点。目前,有关胆汁淤积性肝病的有效治疗药物相对匮乏,中医药治疗胆汁淤积肝损伤(CLI)疗效及其作用机制研究备受关注。常用中药包括清热利湿类、活血化瘀类或凉血化痰类单味药及相关复方,其改善CLI的作用机制研究多聚焦在法尼醇X受体(FXR)、组成型雄甾烷受体(CAR)、早期生长因子-1(EGR-1)、核因子E2相关因子(Nrf-2)等通路。结合当前国内外研究现状,系统地阐述常见中药单味药和复方治疗CLI的药理作用机制,旨在为中药治疗CLI的临床应用提供依据,为中药创新药开发及其深入研究提供参考。