丙泊酚对离体大鼠缺血再灌注心脏PI3K／Akt信号通路及内质网应激凋亡途径的影响  

Effects of propofol on PI3K/Akt signaling pathway and endoplasmic reticulum stress pathway ofapoptosis induced by ischemia-reperfusion in isolated rat hearts

作　　者：刘柳[1] 庞勇[1] 何东伟[1] 刘新伟[1] 

机构地区：[1]医科大学附属第一医院麻醉科(刘柳现在四川省人民医院麻醉科),重庆400016

出　　处：《中华医学杂志》2012年第37期2611-2614,共4页National Medical Journal of China

摘　　要：目的观察丙泊酚对离体大鼠缺血再灌注心脏磷酸肌醇-3-激酶／丝氨酸-苏氨酸激酶（P13K／Akt）信号通路及内质网应激凋亡途径的影响。方法40只雄性SO大鼠离体心脏，运用随机数字表法分为5组（n=8）：对照组（C组）、缺血再灌注组（I／R组）、丙泊酚组（P组）、丙泊酚＋渥曼青霉素（Wortmannin）组（P＋Wort组）、Wortmannin组（Wort组）。使用Langendorff离体心肌灌注装置，除C组外，其余各组均给予全心缺血30min，再灌注120min；P组、P＋Wort组、Wort组分别平衡灌注20min后，于缺血前10min和再灌注初20min分别使用含50μmol／L丙泊酚、50μmol／L丙泊酚＋100nmol／LWortmannin、100nmol／LWortmannin的K-H液灌注。分别观察各组缺血前及再灌注120min时左室心功能变化情况；再灌注末取心肌组织标本，Tunel法检测各组心肌细胞凋亡指数；免疫组化检测半胱氨酸天冬氨酸蛋白酶-12（caspase-12）和CCAAT／增强子结合蛋白同源蛋白（CCAAT／C／EBP homologous protein，chop）的表达；Western blot测定Akt、磷酸化-Akt（p-Akt）蛋白表达。结果再灌注120min后，与I／R组比较，P组左室舒张末压（LVEDP）明显降低，＋dp／dt max明显升高，心肌细胞凋亡[（27．89±1．04）％比（33．70±2．20）％]、caspase-12[（0．1728±O．0096）比（0．2332±0．0114）]和chop[（0．1889±0．0078）VS（0．2407±0．0123）]表达明显减少，p-Akt表达增加，（P〈0．05）。Wortmannin能部分阻断其心肌保护效应（P〈0．05）。结论丙泊酚能抑制离体大鼠缺血再灌注心肌细胞内质网应激凋亡途径，发挥心肌保护作用，PI3K／Akt信号通路参与了其部分保护作用。Objective To explore the effects of propofol on the PI3K/Akt signaling pathway and the endoplasmic reticulum stress pathway of apoptosis induced by ischemia-reperfusion in isolated rat hearts. Methods Forty isolated rat hearts were completely randomly assigned into 5 different groups： control （C）, ischemia/reperfusion （ I/R）, propofol （ P）, propofol plus Wortmannin （ P ＋ Wort） and Wortmannin （W）. The isolated hearts were perfused on a Langendorff apparatus. Except for group C, all hearts were subjected to 30 rain global ischemia and 120 rain reperfusion. In the P, P ＋ W and W groups, 50 μmol/L propofol or 50 μmol/L propofol ＋ 100 nmol/L Wortmannin or 100 nmol/L Wortmannin were respectively added in the K-H buffer to perfuse for 10 rain at pre-ischemia and 20 min at the beginning of reperfusion. The parameters of cardiac function were recorded at pre-ischemia and at the 120 rain of reperfusion. The apoptotic index was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling （Tunel）. The expressions of caspase-12 and CCAAT/C/EBP homologous protein （chop） were measured by immunohistochemistry while those of Akt and p-Akt（Ser473） detected by Western blot. Results Compared with the I/R group, LVEDP significantly deceased and ＋ dp/dtmax significantly increased, the apoptotic index [ （ 27.89 ± 1.04 ） % vs （ 33.70 ± 2. 20） % ], the expressions of caspase-12 [ （ 0. 1728 ± 0. 0096 ） vs （ 0. 2332 ± 0. 0114 ） ] and chop [ （0. 1889 ± 0. 0078 ） vs （ 0. 2407 ± 0. 0123 ） ] significantly deceased while that of p-Akt （ Ser473 ） significantly increased in Group P （ P 〈 0. 05 ） . Wortmannin abolished the partial protective effects of propofolpostconditioning（ P 〈 0. 05 ）. Conclusion Propofol perfusion may attenuate the endoplasmie reticulum stress pathway of apoptosis induced by ischemia/reperfusion in isolated rat hearts partly through the PI3K/ Akt signal pathway.

关 键 词：丙泊酚 凋亡 内质网应激 PI3K/AKT 

分 类 号：R363[医药卫生—病理学]