细菌脂多糖对不同成熟度新生小鼠脑发育的影响  

Effects of Bacterial Lipopolysaccharide on Brain Development of Neonatal Mice at Different Maturity Levels

作　　者：徐发林[1] 庄方莉[1] 白琼丹[1] 段佳佳[1] 

机构地区：[1]郑州大学第三附属医院新生儿科,郑州450052

出　　处：《实用儿科临床杂志》2012年第8期611-613,616,共4页Journal of Applied Clinical Pediatrics

基　　金：2010年河南省卫生厅5451项目;河南省医学科技攻关项目(200803065)

摘　　要：目的探讨细菌脂多糖(LPS)对不同成熟度新生小鼠脑发育的影响。方法 2日龄新生小鼠80只随机分成4组,分别腹腔注射不同剂量(0.3 mg.kg-1、0.6 mg.kg-1、0.9 mg.kg-1)的LPS和等容积的9 g.L-1盐水,观察给药后小鼠的一般情况;测定给药后脑组织IL-6水平、体质量变化以及相对肝质量;2日龄和7日龄的新生小鼠各20只,不同日龄的新生小鼠随机分成感染组(腹腔注射0.6 mg.kg-1LPS)和对照组(腹腔注射等容积的9 g.L-1盐水),连续给药5 d,均至12日龄时,灌注取脑,应用免疫组织化学技术检测各组小鼠脑组织碱性髓鞘蛋白(MBP)、神经元特异性烯醇化酶(NSE)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)的表达情况。结果 0.6 mg.kg-1LPS腹腔注射可导致新生小鼠体质量增长缓慢、肝大、脑组织IL-6水平升高(Pa<0.05),随着LPS剂量增加,病死率增高,IL-6水平未再升高。2日龄感染组小鼠MBP、NSE表达均明显减少,而Caspase-3的表达明显增多(Pa<0.05);7日龄感染组的MBP表达无明显减少(P>0.05),而NSE的表达明显减少,Caspase-3的表达明显增多(Pa<0.05)。结论新生小鼠腹腔注射0.6 mg.kg-1LPS可以模拟临床感染;2日龄新生小鼠感染不仅影响脑白质髓鞘发育,同时也影响灰质神经元;而脑发育相对成熟的7日龄新生小鼠感染主要影响皮质神经元的发育。Objective To explore the effects of bacterial lipopolysaccharide（LPS） on brain development of neonatal mice at different maturity levels. Methods The newborn mice（n=80） of 2 days were randomly assigned into 4 groups,and were injected either with different doses of LPS（0.3 mg·kg-1,0.6 mg·kg-1,0.9 mg·kg-1） or with equal volume of 9 g·L-1 saline.The mice were sacrificed and the relative liver weight vs the body was calculated,and the level of interleukin-6（IL-6） in the brain was measured by using ELISA.Two days and seven-day old mice（each for 20） were randomly divided into infection group（intra-abdominal injection of LPS）and control group（intra-abdominal injection of equal volume 9 g·L-1 of saline）,and each neonatal mouse was injected LPS or 9 g·L-1 of saline for 5 days,and brains were perfused and collected at 12 days.The expression of myelin basic protein（MBP）,neuron specific enolase（NSE） and active Caspase-3 in the brain were detected by immunohistochemistry staining. Results The newborn mice were injected with 0.6 mg·kg-1 of LPS showed growth retardation,liver enlargement and increased IL-6 in the brain（Pa0.05）.Mortality increased with the doses of LPS,but not the levels of IL-6.The expression of brain MBP and NSE levels in two-day-old infected mice were reduced significantly,and the expression of Caspase-3 was increased significantly（Pa0.05）.In seven-day-old infected mice,the expression of NSE was reduced significantly,but not the expression of MBP（P0.05）.The expression of Caspase-3 was increased significantly（P0.05）. Conclusions Newborn mice by intraperitoneal injection of 0.6 mg·kg-1 of LPS can mimic clinical chronic infection.Newborn mice with infection at two days after birth induce both white matter and gray matter injury,but not for seven-day-old newborn mice,the injury is only observed in the cortical neurons only.

关 键 词：细菌脂多糖 神经元特异性烯醇化酶 碱性髓鞘蛋白 

分 类 号：R722.1[医药卫生—儿科]