高原环境下REM睡眠剥夺大鼠的GRP78及caspase-12表达及药物干预  

Expression of GRP78 and capase-12 in rats with sleep deprivation during high-altitude environment and medicine intervention

作　　者：马亚杰[1] 杨金升[1] 郑佳丽[1] 刘学娟[1] 

机构地区：[1]兰州军区兰州总医院神经内科,甘肃730050

出　　处：《脑与神经疾病杂志》2011年第4期276-280,共5页Journal of Brain and Nervous Diseases

摘　　要：目的观察高原与平原不同时间快速眼动睡眠剥夺(REMSD)对大鼠海马区GRP78及Caspase-12的表达变化及人参皂甙Rd(GS Rd)干预作用,探讨GRP78和Caspase-12表达与细胞凋亡的关系以及GS Rd的可能的神经保护作用。方法本试验采用小平台水环境法制作不同时间点大鼠睡眠剥夺(SD)模型,应用免疫组织化学染色检测相关时间点GRP78、Caspase-12蛋白的表达;TUNEL试剂盒检测凋亡细胞。结果在兰州组,与正常睡眠组比较,SD 1d大鼠的GRP78和Caspase-12蛋白表达开始增高,3d时达高峰,5d时与正常睡眠组相比无明显差别。GS Rd干预组大鼠SD 1d、3d GRP78的表达较生理盐水组增高,SD 5d时GRP78的表达与生理盐水组无明显差异;GS Rd干预组大鼠SD 1d、3d Caspase-12的表达较生理盐水组降低,SD 5d时Caspase-12的表达与生理盐水组无明显差异。与兰州组比较,在相同时间点可可西里组GRP78和Caspase-12的表达均增高。结论内质网应激后启动基本自稳调节系统,长期严重的内质网应激使这种自稳作用消失,并启动凋亡通路,这可能是SD造成脑损害的机制之一;高原环境暴露进一步加剧内质网应激;GS Rd可能是通过升高GRP78和降低Caspase-12表达,减轻内质网应激发挥脑保护作用。Objective To observe the changes of GRP78 and caspase-12 expression in the rats＇ hippocampus on different stages of REMSD Ginsenoside Rd in plateau and plain.To discuss association between expression of the GRP78 and the caspase-12 and apoptosis as well as the possible neouruprotective effect of Ginsenoside Rd.Methods At this experiment,SD was induced in Wistar rats by employing ＂flower pot＂ technique.We checked out expression protein of GRP78 and caspase-12 with immunohistochemistry staining,and checked out apoptosis cell with TUNEL.Results Immunohistochemistry staining results showed the expressions of GRP78 and caspase-12 protein increased after one day of REM sleep deprivation compared with those in rats with normal sleep in Lanzhou groups.and reached the highest on the third day.While on the fifth day,the expressions of GRP78 and caspase-12 protein were not different from those of normal sleep group.After intervention of Ginsenoside Rd,the expression of GRP78 were higher than that of physiological saline groups after first or third day of REM sleep deprivation.The expression of GRP78 protein were not different from physiological saline groups on the fifth day.And after intervention of Ginsenoside Rd,the expression of caspase-12 were lower than physiological saline groups after first or third day of REM sleep deprivation.The expression of caspase-12 protein were not different from physiological saline groups on the fifth day.At the same time the expression of GRP78 and caspase-12 protein were higher compared with Lanzhou group in the Kekexili group.Conclusion After endoplasmic reticulum stress,the stable regulation system was primed.But the state state regulation system will be lost after long-term serious endoplasmic reticulum stress,and induced apoptosis proceduring,this is possiblely one of causes that damage brain.High-altitude environment exposure may aggravate endoplasmic reticulum stress.Perhaps Ginsenoside Rd lightens endoplasmic reticulum stress by increasing expression of GRP78 and decreasing

关 键 词：高原环境 睡眠剥夺 葡萄糖结合蛋白78 半胱氨酸门冬氨酸特异性蛋白酶12 人参皂甙RD 

分 类 号：R742.1[医药卫生—神经病学与精神病学]