摘要
目的探讨N-乙酰半胱氨酸(NAC)对内毒素(LPS)增敏的新生大鼠缺氧缺血性脑损伤(HIBD)的防治效果和作用机制。方法8日龄Wistar大鼠98只,性别不拘,其中86只随机分为3组,安慰剂组(29只)、小剂量(25 mg/kg)(31只)和大剂量(200mg/kg)NAC治疗组(26只)。新生大鼠予腹腔注射LPS(0.1 mg/kg),3 d后结扎左侧颈总动脉并吸入7.7%的氧气40 min制备成LPS增敏的HIBD动物模型。在应用LPS后1 h、缺氧缺血(HI)前2 h、HI后02、4 h腹腔注射NAC(25 mg/kg或200 mg/kg)或同体积生理盐水,HI后7 d评价脑损伤的程度。余下12只分别给予大剂量NAC(6只)和安慰剂(6只)并在HI后24 h测定脑组织Caspase-3的活性和蛋白印迹。结果大剂量NAC治疗组脑梗死体积较安慰剂组减少77%(P<0.001),而组织丢失体积均减少67%(P<0.001)。小剂量NAC治疗组脑梗死及脑组织丢失体积与对照组相比无明显差别。HI后24 h大剂量NAC治疗组Caspase-3活性较安慰剂组显著降低(53%,P<0.001)。结论NAC对LPS增敏的新生大鼠HIBD的防治作用呈剂量依赖性,其神经保护作用与抑制Caspase-3相关。
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 poamatal day 8 of either scx 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.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2006年第6期378-381,共4页
Journal of Applied Clinical Pediatrics
基金
Supported by the National Natural Science Foundation of China(30571972)
