PDF(1241 KB)
PDF(1241 KB)
PDF(1241 KB)
宫内感染对早产新生大鼠脑发育的影响
Impact of intrauterine infection on long-term brain development of premature rats
目的：本实验通过对孕鼠腹腔内注射脂多糖（LPS）制备宫内感染动物模型，探讨宫内感染对胎鼠脑神经细胞凋亡及其对早产新生大鼠远期脑发育的影响。方法：妊娠18 d孕鼠随机分为对照组、低剂量感染组和高剂量感染组，对感染组分别给予0.3 mg/kg和0.6 mg/kg LPS腹腔内注射，对照组腹腔注射生理盐水，24 h后处死部分大鼠（n＝7），取胎盘组织行苏木精-伊红染色观察其病理变化、TUNEL法观察胎鼠脑神经细胞的凋亡情况，部分孕鼠继续怀孕至21 d前诱导分娩，将新生早产鼠饲养至42 d行迷宫试验。结果：与对照组比较，宫内感染组孕鼠胎盘组织可见明显的炎性细胞浸润，血管充血等病理改变，感染组胎鼠脑组织神经细胞的凋亡增加（对照组8.00±0.36 vs低剂量感染组32.41±5.36，高剂量感染组66.41±7.61，P＜0.01），且神经细胞的凋亡随着宫内感染的程度加重而增多。感染组大鼠Y型迷宫试验达标所需的训练次数较对照组明显增多（对照组56.8±3.7 vs低剂量感染组117.8±8.7和高剂量感染组194.4±13.7，P＜0.01），记忆保持中正确反应次数明显低于对照组（对照组0.92±0.06 vs低剂量感染组0.62±0.09和高剂量感染组0.37±0.09，P＜0.05）。结论：宫内感染可导致胎鼠脑神经细胞的凋亡，并损伤新生大鼠的学习记忆功能，影响其远期智能发育。［中国当代儿科杂志，2010，12（7）：569-572］
OBJECTIVE: To investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats. METHODS: Eighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42. RESULTS: Obvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41±5.36 in the 0.3 mg/kg infection group and 66.41±7.61 in the 0.6 mg/kg infection group vs 8.00±0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group ［117.8±8.7 (0.3 mg/kg infection group) and 194.4±13.7 (0.6 mg/kg infection group) vs 56.8±3.7 (control group); P<0.01］. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62±0.09 in the 0.3 mg/kg infection group and 0.37±0.09 in the 0.6 mg/kg infection group vs 0.92±0.06 in the control group; P<0.05). CONCLUSIONS: Intrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.［Chin J Contemp Pediatr, 2010, 12 (7):569-572］
宫内感染 / 神经细胞凋亡 / 脑发育 / 胎鼠 / 新生大鼠
Intrauterine infection / Neural cell apoptosis / Brain development / Fetal rats / Neonatal rats
［1］Hermansen MC, Hermansen MG. Perinatal infections and cerebral palsy ［J］. Clin Perinatol, 2006, 33 (2):315-333.
［2］Kumral A, Baskin H, Yesilirmark DC, Erqur BU, Aykan S,Genc S, et al. Erythropoietin attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain ［J］.Neonatology. 2007, 92(4):269-278.
［3］Dammann O, Kuban KCK, Leviton A. Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitation in children born preterm［J］.Ment Retard Dev Disabil Res Rev, 2002, 8(1):46-50.
［4］程秀永, 董慧芳.宫内感染和宫内窒息对早产鼠脑损伤的联合作用［J］.实用儿科临床杂志, 2006, 21(3):849-850.
［5］王跃春.Y型电迷宫在大鼠学习记忆功能测试中的合理运用［J］.中国行为医学科学, 2005, 14(1):69-70.
［6］Schendel D, Schuchat A, Thorsen P.Public health issues related to infection and pregnancy and cerebral palsy［J］.Ment Retard Dev Disabil Res Rev, 2002, 8(1):39-45.
［7］Pirianov G, Waddinqton SN, Lindstrom TM,Terzidou V, Mehmet H, Bennett PR. The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J(2) delays lipopolysaccharide-induced preterm delivery and reduces mortality in the newborn mouse［J］ .Endocrinology, 2009, 150(2)：699-706.
［8］Cai Z, Pan ZO, Pang Y, Evans OB, Rhodes PG. Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopoysacharide administration［J］.Pediatr Res, 2000, 47(1):64-72.
［9］齐志业, 贺湘英, 李琪, 莫亚雄, 梁琨.新生小鼠兴奋毒性脑损伤的神经行为功能研究［J］.中国当代儿科杂志, 2009,11(3):191-193.
［10］钟乐, 王霞, 余小河, 杨于嘉. 新生大鼠缺氧缺血性脑损伤后的远期行为测试［J］.中国当代儿科杂志, 2005, 7（3）:245-248.
［11］Back SA, Luo NL，Borenstein NS, Levine JM, Volpe JJ, Kinney HC.Late oligoden-drocyte progenitors coincide with the developmental window of vulaer-ability for human perinatal white matter injury［J］. J Neurosci, 2001, 21(4):1302-1312
［12］Cai Z, Pang F, Rhodes PG.Chronic ischemia preferentially causes white matter injury in the neonatal rat brain［J］.Brain Res, 2001, 898(1):126-135.
［13］Tsuji M,Wilson MA, Lange MS, Johnton MV. Minocycline worsens hypoxic-ischemic brain injury in a neonatal mouse model［J］.Exp Neurol, 2004,189(3):58-65.
［14］Bell MJ, Hallenbeck JM.Effects of intrauterine inflammation on developing rat brain［J］. Neurosci Res, 2002, 70(4):570-579.
［15］Kannan S, Saadani-Makki F, Muzik O, Chakraborty P, Mangner TJ, Janisse J, et al. Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET［J］. Nucl Med, 2007, 48(6):946-954.
［16］Kaukola T, Satyaraj E, Patel DD, Tchernev VT, Grimwade BG, Kingsmore SF, et al. Cerebral palsy is characterized by protein mediators in cord serum［J］. Ann Neurol, 2004, 55(2):186-194.
［17］Pang Y, Cai Z, Rhodes PG. Effects of lipopolysaccharide on oligodendrocyte progenitor cells are mediated by astrocytes and microglia［J］.J Neurosci Res, 2000, 62(4):510-520.
［18］Patan S.Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling［J］. J Neurooncol, 2000, 50(1-2):1-15.
［19］Debillon T, Gras-Leguen C, Verielle V, Winer N, Caillon J, Roze JC, et al. Interauterine infection induces programmed cell death in rabbit periventricular white matter［J］. Pediatr Res, 2000, 47(6):736-742.
