摘要
目的探讨脓毒症相关性脑病（SAE）远期脑线粒体损伤与氧化应激的关系。方法通过腹腔注射革兰阴性菌脂多糖（LPS）建立脓毒症模型。出现SAE症状的大鼠（SAE组）及对照组大鼠分别在相应时间点进行神经反射评估后处死，取脑组织提取线粒体。通过流式细胞仪检测线粒体膜电位（MMP）及活性氧（ROS），通过酶标仪检测超氧化物歧化酶（SOD）、丙二醛（MDA）、诱导型一氧化氮合成酶（iNOS）和一氧化氮（NO）水平。结果神经反射评估在12h已经开始下降，并缓慢恢复。MMP在腹腔注射LPS后明显下降，48h降至最低，差异有统计学意义（F=75．785，P〈0．05），72h部分恢复；ROS48h明显升高伴随SOD的明显下降，差异均有统计学意义（F=111．274，21．808，P均〈0．05），72h部分恢复；MDA、iNOS和NO48h增加达到峰值，差异均有统计学意义（F=21．955、61．076、21．184，P均〈0．05），72h部分恢复。脓毒症大鼠脑组织线粒体SOD活性与MMP呈强正相关关系（r=0．856，P〈0．05）；脓毒症大鼠脑组织线粒体ROS水平、MDA水平、iNOS活性和NO水平与MMP呈强负相关关系（r=-0．852、-0．890、-0．940、-0．794，P均〈0．05）。结论在SAE模型中，脑线粒体损伤的高峰可能发生在48h左右，氧化应激的明显增强可能是导致远期线粒体功能障碍的原因之一。
Objective To investigate the long - term mitochondrial dysfunction and oxidative stress in a sepsis - associated encephalopathy（SAE） model. Methods To initiate experimental sepsis, male Wistar rats were injected in- traperitoneafly with 10 mg/kg of lipopolysaccharide （LPS） dissolved in sodium chloride. Animals were evaluated by neurologie reflex scores before sacrifice and brain tissues were quickly removed at the indicated time points （0 h for control group and 12,24,48,72 h post injections for SAE groups）. Cerebral mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） were detected by flow cytometer and superoxide dismutase （SOD） , malondialdehyde （MDA） ,inducible nitric oxide synthase （iNOS） and nitric oxide （NO） were determined by using microplate reader. Results Deteriorated neurological reflexes were found since 12 h and recovered slowly. Cerebral MMP in 12 h SAE group was decreased significantly compared with that in the control group. MMP was decreased to the lowest level at 48 h （F = 75. 785 ,P 〈 0.05 ） ,and partly recovered at 72 h . ROS, MDA,iNOS and NO were increased significantly at 48 h （F = 111. 274,21. 955,61. 076,21. 184 ,all P 〈0.05 ） and partly recovered at 72 h. SOD changed controversially with ROS（ F = 21. 808,P 〈 0. 05 ）. SOD showed strong positive linear correlations with MMP （ r = 0. 856, P 〈 0.05 ）, whereas ROS,MDA,iNOS and NO showed strong negative linear correlations with MMP （ r = - 0. 852, - 0. 890, - 0. 940, - 0. 794, all P 〈 0.05 ）. Conclusions These results suggest that long - term brain mitochondrial dysfunction of lipopolysaccharide- induced septic rat is partly affected due to an increase in oxidative stress and has a turning - point near 48 h post injections.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2015年第11期860-862,共3页
Chinese Journal of Applied Clinical Pediatrics
基金
基金项目：国家自然科学基金（81272070）
广东省科技计划项目（20108031600238）
关键词
脓毒症相关性脑病
线粒体功能障碍
氧化应激
远期损伤
Sepsis - associated encephalopathy
Mitochondrial dysfunction
Oxidative stress
Long - term injury
