Therapy Effect of N-Acetylcysteine on Lipopolysaccharide-Sensitized Neonatal Rat with Hypoxic-Ischemic Brain Damage
- VernacularTitle:N-乙酰半胱氨酸对内毒素增敏的新生大鼠缺氧缺血性脑损伤的治疗作用
- Author:
Chun-xia, NIE
;
Xiao-yang, WANG
;
Chang-lian, ZHU
- Publication Type:Journal Article
- Keywords:
hypoxic- ischemic;
neuroprotection;
N acetylcysteine;
lipopolysaccharides
- From:Journal of Applied Clinical Pediatrics
2006;21(6):378-381
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of N- acetylcysteine(NAC) on lipopolysaccharide (LPS) - sensitized neonatal rats with hypoxic- ischemic brain damage(HIBD) and possible mechanism except the antioxidant. Methods With the total number of 98 Wistar pups at postnatal day 8 of either sex was used in this study. There were 86 pups which were divided into three groups to evaluate the brain injury:vehicle group ( n = 29) ,low dose (25 mg/kg) ( n = 31 ) and high dose NAC (200 mg/kg) ( n - 26) treatment group. The pups were injected with LPS(0.1 mg/kg)intraperitoneally 3 days before hypoxic- ischemic(HI) insult. Multiple dose of NAC (25 mg/kg or 200 mg/kg) or vehicle was injected intraperitoneally before and after HI. Brain injury was evaluated 7 days after HI. For the Caspase - 3 activity and immunoblotting analysis, the samples were collected at 24 h after HI treated either with vehicle or high dose NAC ( n = 6 per group). Results The brain injury volume was significantly reduced by high dose NAC (200 mg/kg) treatment compared with that of vehicle (77% reduction, P ＜ 0.001 ). The tissue loss was reduced 67 % ( P ＜ 0.001 ) in high dose NAC treated group compared with that of vehicle. However,there was no significant reduction of brain injury in the low dose NAC treatment group compared with vehicle group. Caspase - 3 like activity measurement showed that the activity decreased 53 % after high dose NAC treatment ( P ＜ 0. 001 ) compared with that of vehicle treatment. The immunoblots showed that the active form of Caspase - 3, 17 kDa band, was abolished by the high dose NAC treatment. Conclusions NAC treatment attenuate LPS - sensitized neonatal HI brain injury is dose dependent. The neuroprotective effect involves Caspase - 3 inhibition.
