褪黑素对细菌脂多糖导致的宫内感染脑损伤的保护作用

Protective effect of melatonin on brain injury of intrauterine infection induced by bacterial lipopolysaccharide

目的:研究褪黑素(melatonin,MT)对宫内感染胎鼠脑组织自由基的影响,探讨MT对宫内感染胎鼠脑组织的保护作用。方法:通过给孕鼠腹腔注射细菌脂多糖(lipopolysaccharide,LPS),造成宫内感染脑瘫动物模型,并行MT干预。选用妊娠第19天SD大鼠随机分为空白对照组、宫内感染组和MT处理组,宫内感染组孕鼠缓慢腹腔注射LPS500μg/kg,MT处理组孕鼠腹腔注射LPS 500μg/kg+MT 10 mg/kg。将各大组孕鼠根据注药后观察时间不同,平均分为注药后2 h、6 h、12 h 3小组,各小组4只孕鼠。各小组于相应的时间点迅速处死,于冰盒上剖腹取胎鼠脑组织,分别测定脑组织匀浆的超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量,HE染色观察组织病理变化,并比较各组之间的差异。结果:宫内感染组较空白对照组胎鼠脑组织中SOD、GSH-Px活力下降,MDA含量上升;同时随着感染时间的延长,上述改变亦趋于明显,差异有统计学意义。与宫内感染组相比,MT处理组能提高胎鼠脑组织中SOD、GSH-Px活力,降低MDA含量。结论:宫内感染胎鼠脑组织在宫内已出现自由基蓄积而自身清除力不足,导致胎鼠脑组织损伤,并随着感染时间的延长而脑损伤逐渐加重。褪黑素能对宫内感染胎鼠脑损伤有抗氧化和较强的自由基清除作用,有神经保护作用。

Objective：To investigate the effect of melatonin on free radical in brain tissues of fetal rats with intrauterine infection,explore the protective effect of melatonin on brain tissues of fetal rats with intrauterine infection. Methods：The models of cerebral palsy rat induced by intrauterine infection were established by injecting bacterial lipopolysaccharide into pregnant rats,melatonin intervention was carried out;the SD rats on the 19th day after pregnancy were selected as blank control group,intrauterine infection group and melatonin treatment group;the pregnant rats in intrauterine infection group were treated with intraperitoneal injection of bacterial lipopolysaccharide（500 μg/kg）,and the pregnant rats in melatonin treatment group were treated with intraperitoneal injection of bacterial lipopolysaccharide（500 μg/kg） and melatonin（10 mg/kg）;then the rats in each group were divided into 2-hour group,6-hour group and 12-hour group according to different observing times,4 pregnant rats in each group;the pregnant rats in each group were executed at corresponding time points,then the brain tissues of fetal rats were obtained;the superoxide dismutase（SOD） activity,glutathione peroxidase（GSH-Px） activity and malondialdehyde（MDA） content in the brain tissues of fetal rats after homogenate were detected;HE staining was used to observe the pathological changes of brain tissues,and the differences among different groups were compared. Results：Compared with blank control group,SOD activity and GSH-Px activity of brain tissues of fetal rats in intrauterine infection group decreased,MDA content increased;with the extension of infection time,the above-mentioned changes became more obvious,there was significant difference;compared with intrauterine infection group,SOD activity and GSH-Px activity of brain tissues of fetal rats in melatonin treatment group increased,MDA content decreased. Conclusion：Brain injury of fetal rats with intrauterine infection may be induced by intrauterine excessive free radicals and insufficient self-clearance,which deteriorates with the extension of infection time;melatonin has neuroprotective effect based on antioxidation effect and strong free radicals scavenging effect.