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目的 探讨远志皂苷对宫内感染所致胎鼠脑白质损伤(WMD)的神经保护作用及相关机制。方法 孕鼠腹腔注射脂多糖(LPS)复制宫内感染所致WMD仔鼠模型。孕鼠随机分为空白对照组(NS组)、模型组(LPS组)、地塞米松组(Dex组)及远志皂苷组(TEN组)，新生仔鼠组别与孕鼠组别对应。HE染色观察仔鼠脑组织，母鼠胎盘和子宫的形态变化；斜坡实验、悬吊实验及拒俘实验检测仔鼠学习记忆能力；IHC方法观测仔鼠胼胝体离子钙结合适配器分子1(IBA-1)、O4的变化，Western blot法检测胼胝体髓鞘碱性蛋白(MBP)、抗髓磷脂蛋白脂质蛋白(MPLP)的表达，ELISA法检测各阶段仔鼠胼胝体炎性因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)的变化。结果 HE染色结果表明LPS成功构建了宫内感染所致WMD胎鼠模型；四组孕鼠给药后进食及活动正常，NS组、LPS组、Dex组和TEN组各获得合格仔鼠90只、89只、96只及126只。与NS组相比，LPS组仔鼠的斜坡实验、悬吊实验及拒俘实验评分降低，LPS组O4、MBP、MPLP的表达量均明显降低，IBA-1、IL-1β、IL-6、TNF-α的表达量明显增高；与LPS组相比，Dex组和TEN组各实验评分均增加，O4、MBP、MPLP的表达量增高，IBA-1、IL-1β、IL-6、TNF-α的表达量明显降低。结论 远志皂苷抑制M1型小胶质细胞活性减少炎性因子释放，从而促进少突胶质细胞成熟分化形成髓鞘，改善了WMD仔鼠的神经行为学表现。
Abstract：Objective To determine the neuroprotective effect of tenuigenin on white matter damage (WMD) in fetal rats induced by intrauterine infection and related mechanisms.Methods Pregnant rats were intraperitoneally injected with lipopolysaccharide (LPS) to replicate the intrauterine infection induced WMD model.Pregnant rats were randomly divided into a blank control group (NS group),a model group (LPS group),a dexamethasone group (Dex group) and a farnesoid saponin group (TEN group),and the neonatal litter groups corresponded to the groups of pregnant rats.The morphological changes in the brain tissue,placenta and uterus of the littermates were observed by HE staining;and the learning and memory abilities of the pups were examined with the ramp test,the suspension test,and the capture refusal test.Changes of ionized calcium-binding adapter molecule 1 (IBA-1) and oligodendrocyte marker 4 (O4) in the corpus callosum of the pups were observed by IHC.Myelin basic protein (MBP) and myelin proteolipid protein (MPLP) proteins were detected in the corpus callosum by Western blot;and changes in inflammatory factors interleukin-1 beta (IL-1β),interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) in the corpus callosum of the rats at each stage of pregnancy were detected by ELISA.Results HE staining of the placenta,uterus and brain tissues of female rats in the NS group and LPS group showed that LPS successfully constructed a fetal rat model of intrauterine infection WMD;the four groups of pregnant rats had normal feeding and activities after the injection.The NS group,the LPS group,the Dex group and the TEN group each obtained 90,89,96 and 126 qualified pups.Compared with those of the NS group,the scores of slope test,suspension test,and capture refusal test of littermates in the LPS group were lowered,the expressions of O4,MBP,and MPLP were markedly lowered,and the expressions of IBA-1,IL-1β,IL-6,and TNF-α were obviously higher in the LPS group.Compared with those of the LPS group,all experimental scores increased in the Dex group and TEN group,the expressions of O4,MBP,and MPLP increased,and that of IBA-1,IL-1β,IL-6,and TNF-α decreased greatly.Conclusion Tenuigenin can inhibit the activity of M1 microglia and reduce the release of inflammatory factors,thus promoting the maturation and differentiation of oligodendrocytes and the formation of myelin sheath to improve the neurobehavioral performance in offspring rats with WMD.
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基本信息:
中图分类号:R285.5
引用信息:
[1]王堰,赵红梅,邢淑荣,等.远志皂苷对宫内感染致胎鼠脑白质损伤的神经保护作用及机制研究[J].中南药学,2026,24(01):5-11.
基金信息:
国家自然科学基金面上项目(No.82474101); 无锡市卫生健康“三名”战略人才项目-中青年医疗卫生拔尖人才培养计划(No.BJ2023094)
2025-04-16
2025
2025-12-17
2025
1
2026-01-20
2026-01-20