Therapy Effect of N-Acetylcysteine on Lipopolysaccharide-Sensitized Neonatal Rat with Hypoxic-Ischemic Brain Damage / 实用儿科临床杂志

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 injuryvehicle 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.