Protective effect of CpG-ODN conditioning on hypoxic/ischemicbrain damage in neonatal rats
10.3969/j.issn.1001-1978.2017.07.014
- VernacularTitle:CpG-ODN对新生大鼠缺血/缺氧性脑损伤的保护作用研究
- Author:
Ying HUANG
;
Lan YE
;
Zhanhui FENG
;
Shiping WANG
;
Zhuting FENG
;
Yanling JIN
- Keywords:
hypoxic/ischemic brain damage;
cerebral;
TNF-α;
TLR9;
CpG-ODN;
p38 mitogen activated protein kinase
- From:
Chinese Pharmacological Bulletin
2017;33(7):956-961
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study the therapeutic effect of CpG-ODN, an agonist of Toll-like receptor 9 (TLR9), on hypoxic/ischemic encephapathy in neonatal rats and investigate the mechanisms.Methods Fifty healthy 7-day-old neonatal Wistar rats (in either gender, weighing 12~17g) were randomly divided into sham operation group, HIBD group, and CpG-ODN low group(0.35 mL·kg-1), CpG-ODN middle group(1.40 mL·kg-1), CpG-ODN high group(5.60 mL·kg-1).The neurological function was scored after 48h operation;ten rats of each group was executed respectively and brains tissue was taken;HE staining was used to observe the brain pathological changes.Western blot assay was used to detect the expressions of TLR9 and phosphor-p38 mitogen-activated protein kinases(p-p38 MAPK), and enzyme linked immunosorbent assay (ELISA) method was adopted to detect TNF-α expression.Results The CpG-ODN low, middle group were improved in impairment significantly compared with the HIBD group, and the brain pathological change was lessened, while the CpG-ODN high group was impaired significantly compared with the HIBD group (P<0.05), and brain pathological change was sharpened.Western blot showed the up-regulation in TLR9 and p-p38 MAPK and a significant increase of the expression of TNF-α in the brain tissue in CpG-ODN group with statistical difference in HIBD group and sham operation group(P<0.05).Conclusions The neuro-behavioral score and nervous system function can be improved and the hypoxic/ischemic brain damage can be reduced in neonatal rats in the CpG-ODN low, middle group.The protective mechanisms may be suitably via activating p38 MAPK signaling pathway to promote p38 MAPK phosphory1ation and up-regulation of the expression of TNF-α in the brain tissue of rats.
