Inosine improves offspring white matter injury caused by infection in pregnant rats via regulating astrocytes
10.16557/j.cnki.1000-7547.2024.04.003
- VernacularTitle:肌苷通过调节星形胶质细胞改善孕期感染导致的子代大鼠白质损伤
- Author:
Yong HAN
1
;
Xin LI
;
Jin CHEN
;
Jinping SUN
;
Quanrui MA
Author Information
1. 宁夏医科大学基础医学院人体解剖与组织胚胎学系,银川 750004
- Keywords:
inosine;
periventricular leukomalacia(PVL);
myelin;
astrocyte;
rat
- From:
Chinese Journal of Neuroanatomy
2024;40(4):421-428
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The aim of this study is to examine the impact of inosine pretreatment in pregnant rats on as-trocyte(Ast)responses in the maternal inflammation-induced periventricular leukomalacia(PVL)model in offspring.Methods:The pregnant rats were divided into Control,PVL,and IN-PVL groups.In the PVL group,pregnant rats at gestational day 17(E17)received intraperitoneal injections of lipopolysaccharide(LPS)at a dose of 350 μg/kg for 2 days.In the IN-PVL group,pregnant rats at E1 were administered an inosine solution(1 mg/ml,25 ml/day)for 16 days followed by intraperitoneal injections of LPS for 2 days.Newborn 7-day-old rat brains from each group of pregnant rats were collected,and the protein expression of myelin basic protein(MBP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),glial fibrillary acidic protein(GFAP),complement 3(C3),S100 calcium binding protein A10(S100A10),platelet-derived growth factor(PDGF),chemokine ligand 1(CXCL1),and connexin 43(Cx43)were detected by immunofluorescence staining or Western Blot.Results:The PVL group exhibited a decrease in myelin MBP color area and an increase in hypertrophic Ast in contrast to the Control group.Additionally,protein expression levels of proinflammatory factors(TNF-α,IL-6,IL-1β),GFAP,A1 Ast marker C3,and Ast linker Cx43 were significantly elevated in the PVL group compared to the Control group(P<0.05).Conversely,protein expression levels of anti-inflammatory factors(IL-4,IL-10),MBP,A2 Ast marker S100A10,and Ast secreted products(PDGF,CXCL 1)were significantly decreased in the PVL group com-pared to the Control group(P<0.05).Inosine pretreatment effectively reversed the expression levels of these proteins(P<0.05).Conclusion:Inosine pretreatment of pregnant rats improved cerebral hypomyelination in offspring PVL neonatal rats by regulation of Ast responsiveness and the secretion of pro-myelinating substances.