title: Effects of that ATRA inhibits Nrf2-ARE pathway on glial cells activation after intracerebral hemorrhage.
abstract: Previous studies indicate that the Nrf2-ARE signaling pathway plays a neruo-protective role in glia cell, however, the mechanism was also elusive. This study aims to explore the inhibitive function of all-trans-retinoic (ATRA) on Nrf2-ARE pathway in intracerebral hemorrhage (ICH), and investigate the mechanism. In this study, the femoral artery injection method was employed to establish ICH model. The model rats were randomly divided into four groups, including Sham group, ICH group, ATRA group and DMSO group. The neurological scores were evaluated for the four groups at different time points. Hematoxylin-Eosin staining was used to stain the CD11b positive glia cells. Double immunofluorescence staining method was utilized to observe the co-expression of HO-1, NF-κB, Nrf2 and TNF-α and CD11b marker in glia cells. Western blot assay was used to detect the Nrf2 protein (total and binding Nrf2), HO-1, NF-κB and TNF-α proteins in every group. The results indicated that neurologiclal scores were significantly decreased in ATRA group compared to ICH gorup (P < 0.05). The glia cells were significantly activated and accumulated in ICH rats. ATRA significantly decreased co-expression of Nrf2, HO-1 and CD11b, and increased co-expression of NF-κB, TNF-α and CD11b of glia cells. ATRA significantly decreased total Nrf2 expression and increased binding Nrf2 expression in ATRA group compared to ICH group (P < 0.05). ATRA decreased anti-oxygen protein Nrf2 and HO-1, and increases inflammatory factors NF-κB and TNF-α. In conclusion, the application of ATRA could inhibit the neuro-protective function effectively by blocking the Nrf2-ARE pathway in glia cells.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Nanchang University Nanchang, China ; Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yin
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Nanchang University Nanchang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Nanchang University Nanchang, China ; Department of Neurology, Sixth Hospital of Wuhan Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Bao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D014212:Tretinoin; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase
keywords: Intracerebral hemorrhage; Nrf2-ARE pathway; all-trans-retinoic; glia cells