Up-regulated expression of NT-3 attenuates cerebral ischemia/reperfusion injury in rats
- VernacularTitle:HRE介导的NT-3表达上调减轻大鼠局灶性脑缺血再灌注损伤
- Author:
Junfeng ZHANG
;
Lili SHI
;
Li ZHANG
;
Hongbo LI
;
Jianshui ZHANG
;
Cunfang QI
;
Yong LIU
;
Xi XU
- Publication Type:Journal Article
- Keywords:
hypoxia-inducible gene expression;
neuroprotection;
ischemic stroke;
gene therapy
- From:
Basic & Clinical Medicine
2015;(9):1199-1204
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the neuroprotective effects of neurotrophin-3 (NT-3) expression controlled by five copies of the hypoxia-responsive elements after focal cerebral ischemia .Methods Three groups of rats re-ceived RV-5H-NT3, RV-5H-EGFP or saline injection .Three days after gene transfer , the rats underwent 90 min of transient middle cerebral artery occlusion ( tMCAO) , followed by 1-28 days of reperfusion .Immunohistostaining and western blotting were performed to detect ischemia/hypoxia-regulated expression of NT-3 controlled by HRE . The volume of brain infarction and the apoptosis were analysised by TTC and TUNEL staining .The neurological scoring was determined by neurological behavior tests .Results Three days after tMCAO , brain NT-3 expression was significantly increased in the RV-5HNT3-transduced animals compared with the RV-5H-EGFP or saline group (P<0.05), and brain infarct volume was smaller in the RV-5H-NT3-transduced group than the RV-5H-EGFP or saline group ( P<0.05 ) .The percentage of TUNEL-positive cells was reduced in RV-5 H-NT3-transduced brains compared with the RV-5 HEGFP or saline group 3 and 7 days after tMCAO ( P<0.05 ) .Furthermore , the neurolog-ical status of RV-5H-NT3-transduced rats was better than that of RV-5H-EGFP-or saline-transduced animals from 1 day to 4 weeks after tMCAO ( P<0.05 ) .Conclusions HRE may modulate NT-3 expression in the ischemic brain tissue and that the up-regulated NT-3 may effectively improve neurological status following tMCAO due to de-creased initial damage .
