发育期大鼠反复高热惊厥激活内质网应激
首发时间:2008-01-04
摘要:目的 研究反复高热惊厥(febrile seizures,FS)对发育期大鼠ACTH及葡萄糖调节蛋白78(glucose-regulated protein 78,Grp78)的影响,探讨FS与内质网应激的关系。方法 40只21日龄SD大鼠,采用热水浴诱导大鼠惊厥,隔日1 次,共10 次。大鼠随机分为两组: 正常对照组和高热组, 根据惊厥与否进一步将高热组分为高热对照组和反复FS组。采用放射免疫分析法测定各组大鼠血浆中ACTH水平,用免疫组织化学法和蛋白免疫印迹 (Western blotting) 检测各组大鼠大脑皮层和海马神经元Grp78蛋白的表达水平。结果 与对照组和高热组比较,反复FS组大鼠血浆ACTH水平显著升高(P﹤0.01),皮层及海马Grp78蛋白表达也明显增强。结论 反复FS可引起下丘脑-垂体-肾上腺皮质轴(HPA)激活,诱导脑内Grp78 蛋白表达增加,导致内质网应激。
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Endoplasmic reticulum stress activated by recurrent febrile seizures in developing rats
Abstract:Objective The present study aimed to explore the association between recurrent febrile seizures and endoplasmic reticulum stress in the brain of developing rats. Method Forty Sprague-Dawley rats aged 21 days were randomly divided into control group (immersed in 37. 0℃ water, n=12) and hyperthermia treated group (immersed in 44. 8℃ water, n=28), which was subdivided into hyperthermia group (n=12) and seizures group (n=16) according to whether seizures occurred or not. Seizures were induced ten times in a bath of warm water, once every 2 days. The plasma content of ACTH was detected by radioimmunoassay. The protein level of Glucose-regulated protein 78 (Grp78) was examined by immunohistochemistry staining and Western blotting. Result After recurrent seizures, the plasma content of ACTH was increased significantly in seizures group compared with that in control group ( P < 0. 01). The expression of Grp78 in cortex and hippocampal was obviously upregulated in seizures group compared with those in control group and hyperthermia group. Conclusion Recurrent febrile seizures could activate Hypothalamic-pituitary-adrenocortical axis (HPA) and increase the expression of Grp78, which demonstrated the endoplasmic reticulum stress was activated.
Keywords: Febrile seizures Glucose-regulated protein 78 Endoplasmic reticulum stress
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No.1776417927211994****
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