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18d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0.3mg/kg和0.6mg/kgLPS腹腔内注射,对照组腹腔注射生理盐水,24h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21d前诱导分娩,将新生早产鼠饲养至42d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±0.36vs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±3.7vs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±0.06vs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。

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.