丙酮酸乙酯对宫内感染致脑损伤新生仔鼠AQP4表达和脑组织超微结构的影响

Effects of ethyl pyruvate on expression of aquaporin-4 and ultrastructure changes in neonatal rats with brain damage caused by intrauterine infection

目的研究丙酮酸乙酯(EP)对宫内感染致新生仔鼠脑损伤水通道蛋白4(AQP4)表达和脑组织超微结构的影响。方法选取36只孕鼠随机分为LPS组(n=12)、EP组(n=12)、NS组(n=12)。LPS组:孕17d、18d连续两天腹腔注射LPS 380μg/kg;EP组:同法制备孕鼠宫内感染模型,并在注射LPS后立即给予孕鼠腹腔注射EP 40mg/kg;NS组:腹腔注射同等量生理盐水。对孕鼠分娩后的胎盘和新生仔鼠脑组织进行HE染色观察宫内感染和脑损伤情况。剔除早产鼠,各组随机选取新生仔鼠36只,于生后12、24、48h对脑组织进行免疫组织化学染色,观察AQP4的表达;电镜观察脑组织超微结构的变化。结果与NS组比较,LPS组孕鼠胎盘组织可见大量的炎性细胞浸润,有宫内感染,LPS组仔鼠HE染色提示有脑损伤;与LPS组相比较,EP组仔鼠出生后24h、48h脑组织AQP4的表达量均低于LPS组(P<0.05);电镜下LPS组神经细胞超微结构显示损伤严重。结论丙酮酸乙酯对宫内感染致脑损伤新生仔鼠的脑组织具有一定的神经保护作用,可能与AQP4表达水平有关。

Objective To study the effect of ethyl pyruvate（EP）in the expression of aquaporin-4（AQP4）and ultrastructure changes in neonatal rats with brain damage caused by intrauterine infection. Methods A total of 36 pregnant Wistar rats were enrolled in this study,and were divided into lipopolysaccharide（LPS）group,EP group and normal saline（NS）group,with 12 rats in each group.LPS group was consecutively injected with LPS（380μg/（kg·d）intraperitoneally,EP group were consecutively injected with lipopolysaccharide intraperitoneally,and EP was administrated intraperitoneally at a dose of 40 mg/kg immediately.NS group was injected with normal saline intraperitoneally as control group.After the delivery of pups,thirty-six pups were selected.Placenta of rats were taken for hematoxylline-eosin（HE）staining to confirm its intrauterine infection in 12 hours,24 hours,48 hours after birth.Aquaporin-4 expression in brain tissue was studied through immunohistochemical analysis.Ultrastructure changes in damaged brain and control group were studied electron-microscopically. Results Obvious pathological changes were observed in the placenta of LPS group.The expression level of AQP4 was lower in EP group and NS group in 24 hours and 48 hours after birth than that in LPS group（P〈0.05）.LPS group nerve cells ultrastructure showed serious injury. Conclusion Ethyl pyruvate has neuro-protective effect on LPS-induced brain injury,and may be associated with the expression level of AQP4.