Yoon B H, Kim C J, Romero R, Jun J K, Park K H, Choi S T, Chi J G
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Korea.
Am J Obstet Gynecol. 1997 Oct;177(4):797-802. doi: 10.1016/s0002-9378(97)70271-0.
Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit.
Rabbits with timed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (70%). Animals were allocated in a ratio of 2:1 for inoculation with either Escherichia coli (0.2 ml containing 10(3) to 10(4) colony-forming units) or sterile saline solution. Both groups were treated with ampicillin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hours until they were killed 5 to 6 days after hysteroscopy. Histologic examination of the placentas and fetal brains was conducted.
Forty-five animals underwent hysteroscopy; 31 were inoculated with E. coli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were fewer live fetuses in the E. coli-inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli-inoculated rabbits but none in the saline solution group (p < 0.05). All rabbits with brain white matter lesions had evidence of intrauterine infection. Evidence of white matter damage included increased karyorrhexis, rarefaction, and disorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies.
Experimental ascending intrauterine infection can cause fetal brain white matter lesions.
脑室周围白质软化是早产儿常见的脑白质病变，是脑瘫的主要危险因素。流行病学研究表明感染与脑室周围白质软化之间存在关联。本研究的目的是确定上行性宫内感染是否会导致胎兔脑白质病变。
对妊娠时间明确的兔子在妊娠20至21天时进行宫腔镜检查（70%）。动物按2:1的比例分配，分别接种大肠杆菌（0.2 ml含10³至10⁴菌落形成单位）或无菌盐溶液。两组均每8小时用氨苄西林-舒巴坦（优立新，每日100 mg/kg；辉瑞，首尔）治疗，直至宫腔镜检查后5至6天处死。对胎盘和胎儿大脑进行组织学检查。
45只动物接受了宫腔镜检查；31只接种大肠杆菌，14只接种无菌盐溶液。在处死动物时，接种大肠杆菌的动物宫内感染率更高，活胎数量比盐溶液组少。在10只接种大肠杆菌的兔子所生的12只胎儿中发现了脑白质损伤的组织学证据，而盐溶液组未发现（p<0.05）。所有有脑白质病变的兔子都有宫内感染的证据。白质损伤的证据包括核碎裂增加、白质稀疏和结构紊乱。免疫组织化学研究证实在白质损伤区域存在细胞凋亡。
实验性上行性宫内感染可导致胎儿脑白质病变。
