Research on the expression of aquaporin 9 gene and efficacy of mannitol in neonatal rats with hypoxia-ischemic brain edema
10.3760/cma.j.issn.2096-2932.2018.05.013
- VernacularTitle:缺氧缺血后脑水肿与水通道蛋白9表达及甘露醇作用相关机制研究
- Author:
Fanghui WANG
1
;
Shuzhen JIAO
;
Shujuan FAN
;
Ting AI
;
Mi XIAO
;
Xiaojie LIN
;
Li LIU
Author Information
1. 710061,西安交通大学第一附属医院新生儿科
- Keywords:
Hypoxia-ischemia,brain;
Brain edema;
Blood-brain barrier;
Aquaporin 9;
Mannitol
- From:Chinese Journal of Neonatology
2018;33(5):376-380
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the relationship between aquaporin 9 (AQP 9) gene and brain edema in neonatal rats of hypoxic-ischemic brain damage (HIBD) and the therapeutic mechanism of mannitol.Method Healthy and 7-day-old SD rats were randomly assigned into three groups:sham-operated group,HIBD group and mannitol group.Both HIBD and mannitol group were established on HIBD model.The mannitol group was given mannitol intraperitoneally at 0,24,48 h of HIBD.2 ml/kg of 2% Evans blue (EB) were injected intraperitoneally before sacrifice.0,6,12,24,48 and 72 h after HIBD,the outcomes were analyzed including the brain water content,the expression of AQP 9 mRNA measured using RT-PCR and immunofluorescence staining methods,and the permeability of blood-brain barrier (BBB) measured with EB.Result In HIBD group,the brain water content was higher comparing with sham-operated group at 0 h after HIBD(P < 0.05),and gradually increased over time,reaching peak at 48 h (89.3% ± 1.9%) and then decreased.In mannitol group,brain water content started to decrease from 1 h after mannitol administration to the bottom at 12 h (86.5% ±0.6%),then increased to peak at 72 h (87.2% ± 1.7%),and brain water content were decreased during 0 ~ 48 h comparing with HIBD group.HIBD group's EB were higher than sham-operated group (P < 0.05);Mannitol group's EB were decreased comparing with HIBD group (except 0 h,P < 0.05).AQP 9 mRNA expression in the HIBD group was decreased at 0 h,and reached the bottom at 48 h (0.09 ± 0.07).Comparing with sham-operated group,it was higher in the HIBD group at0,6,72 h,and lower (P< 0.05) at 12,24,48 h.Higher AQP 9 mRNA expression were detected in mannitol group than HIBD group and sham-operated group at each time point (with the exception of 48 h) (P < 0.05).AQP 9,which was closely related to water metabolism,were widely found in the pia mater and ependyma using immunofluorescence staining.After ischemia and hypoxia insult,an increasedecrease-increase pattern of AQP 9 expression was found.Conclusion AQP 9 is widely existed in various parts of the brain,influencing brain edema through a variety of pathways.AQP 9 also plays a role in alleviating brain edema in mannitol therapy.