二氮嗪对低温保存后大鼠肾脏的GRP78和CREB2表达的影响  

Diazoxide Affects the Expression of GRP78 and CREB2 in Rats' Kidneys after Hypotheric Perservation

作　　者：徐麟皓[1] 王双燕[1] 殷劲[1] 王妨妨[1] 施敏[1] 张晓明[1] 

机构地区：[1]浙江大学医学院人体解剖与细胞生物学系,杭州310058

出　　处：《中国细胞生物学学报》2010年第2期229-234,共6页Chinese Journal of Cell Biology

基　　金：浙江省科技厅科研项目(No.2007C33026)资助~~

摘　　要：为研究二氮嗪(diazoxide,DE)在大鼠肾脏低温保存的作用及其可能的机制,48只大鼠随机分为对照组(单纯Celsior液冷保存)、实验组(Celsior液中含20μmol/L DE),两组均分别冷保存0、24、48 h。观察肾脏在低温条件下分别保存0、24、48 h后,肾组织丙二醛(malonaldehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性以及葡萄糖调节蛋白78(glucoseregulated protein-78,GRP78)和环磷腺苷反应元件结合蛋白2(cyclic AMP response element bindingprotein-2,CREB2)表达的变化。结果表明,与Celsior组相比,DE组的MDA含量在24 h、48 h这两个时间段明显降低(P<0.01,P<0.05),SOD的酶活性在48 h时间段里明显升高(P<0.05)。免疫组化和Western印迹结果显示,实验组中GRP78和CREB2在24 h、48 h这两个时间段表达都高于对照组(P<0.05)。结果表明含DE的Celsior液较单纯Celsior液对低温保存的离体大鼠肾脏有更好的保护作用,其机制可能是启动内质网应激来保护肾脏功能。To investigate the protective effect of diazoxide （DE） on rat＇s kidneys suffered from hypothermic preservation and the possible mechanisms. Forty-eight SD rats were randomly divided into six groups （n=8）： control group （Celsior cardioplegic solution） with preservation 0, 24, 48 h, and experiment group （20 μmol/L DE in the Celsior cardioplegia） with preservation 0, 24, 48 h. The quantity of malonaldehyde （MDA） and the activity of superoxide dismutase （SOD） of the kidneys of each group were measured after 0, 24, 48 h, and we also observed the expressions of glucose regulated protein-78 （GRP78） and cyclic AMP response element binding protein-2 （CREB2） on rat kidney after hypothermic preservation by immunohistochemistry and Western blot at that times. Compared with the control group, the quantity of MDA was significantly lower in experiment group in 24 h and 48 h respec- tively （P〈0.01, P〈0.05）, the activity of SOD was significantly higher in experiment group （48 h） （P〈0.05）, and the expression of GRP78 and CREB2 were higher in experiment group in 24 h and 48 h respectively （P〈0.05）. This study demonstrates that DE can reduce rat renal injury via up-regulation of GRP78 and CREB2. The effects of DE could initiate the endoplasmic reticulum stress to protect the kidney.

关 键 词：二氮嗪 肾脏 低温保存 GRP78 CREB2 

分 类 号：Q813[生物学—生物工程]