HMGB1在高温致金黄地鼠神经管畸形神经上皮细胞中的表达变化

The expressional changes of HMGB1 in the neuroepithelial cells of neural tube defects induced by hyperthermia in golden hamsters

为了探讨高温致神经管畸形(NTDs)作用的分子机制,为预防人类NTDs的发生提供理论依据,本研究在高温致金黄地鼠NTDs模型的基础上,研究HMGB1在高温致金黄地鼠NTDs神经上皮细胞中的表达变化。将孕鼠随机分为实验组和对照组,分别于水浴处理后8、16、24、40、64 h(相当于胚龄第8、8.5、9、9.5、10.5 d)处死孕鼠,剖腹取鼠胚,制备石蜡切片,应用免疫荧光染色技术检测NTDs发生过程中HMGB1在神经上皮细胞中的表达变化。结果显示:对照组和模型组孕鼠在水浴处理后8、16、24h,HMGB1免疫阳性产物分布于鼠胚神经上皮细胞和周围间充质细胞的胞浆中;水浴后40、64 h,HMGB1表达部位出现了由胞浆向胞核的转移;高温处理后,HMGB1在实验组各期胚胎神经上皮细胞内的表达均比对照组减弱。上述结果提示,HMGB1的表达变化与神经管发育密切相关,其表达降低是高温致神经管畸形发生的重要途径之一。

In order to explore the molecular mechanism of neural tube defects （NTDs） induced by hyperthermia, which may provide a theoretical basis for the prevention of human NTDs. On the base of establishing the hyperthermia-induced golden-hamster NTDs model,the expressional changes of HMGB1 in the neuroepithelial cells during the occurrence of NTDs were investigated. The pregnant rats were randomly divided into the experimental and control groups. The pregnant rats were sacrificed at 8,16,24,40,64 hours （ corresponded the embryonic 8,8.5,9,9.5 and 10.5 days of age） after water bath treatment, then the fetuses were got. After conventional paraffin-embedded, the expression of HMGB1 in the neuroepithelial cells during the occurrence of NTDs were detected using immunofluorescent staining technique. The results showed that in the control and experimental groups, HMGB1 immunoreactivity was all diffusely distributed in the cyto- plasm of neuroepitbelial cells and mesenchymal cells surrounded the neural tube at 8,16 and 24 hours after water bath treatment. At 40 and 64 hours,the expressional place of HMGB1 emerged from the cytoplasm to the nucleus. After maternal hyperthermia,the staining intensity of HMGB1 immunoreactivity in the neuroepithelia at each experimental group was weaker than that of control group. The above results sug- gest that the expressional change of HMGB1 is closely linked to the development of the neural tube, and the decreased expression of HMGB1 may be involved in one of the important ways on hyperthermia-induced NTDs.