丙泊酚预处理对大鼠心肺复苏后脑内质网应激的影响

Effect of propofol pretreatment on endoplasmic reticulum stress in rat brain after cardiopulmo-nary resuscitation

目的：了解丙泊酚（propofol）预处理对心肺复苏（CPR）后大鼠脑损伤及脑内质网应激（endoplasmic reticulum stress，ERS）的影响。方法45只SD雄性大鼠随机分为三组：①假手术组（Sham）；②中长链脂肪乳组（Intralipid）：经皮电刺激心外膜法诱导心脏骤停（cardiac arrest， CA），CA持续6 min后进行CPR至自主循环恢复（ROSC），CA前30 min，腹腔注射中长链脂肪乳（剂量同丙泊酚中长链脂肪乳）；③丙泊酚中长链脂肪乳组（Propofol）：CA前30 min，腹腔注射丙泊酚中长链脂肪乳（10 mg/kg），其余操作同 Intralipid 组。ROSC 后24 h 观察大鼠生存情况并进行神经缺损评分；取脑组织行苏木素-伊红（HE）染色及TUNEL 染色，观察海马CA-1区神经细胞结构损伤及凋亡情况；Western-blot法检测海马GRP78、XBP-1、CHOP及caspase-12蛋白表达。结果①与Sham组比较，Intralipid组与Propofol组大鼠神经缺损评分明显上升（P＜0.05），海马CA-1区HE染色出现不同程度的病理损伤，凋亡神经细胞比例明显升高（P＜0.01）；与Intralipid组比较，Propofol组大鼠神经缺损评分明显下降（P＜0.05），海马CA-1区病理损伤明显改善，凋亡神经细胞比例明显减少（P＜0.01）；②Western blot 检测显示，与 Sham 组比较，Intralipid 组与 Propofol 组大鼠海马GRP78、XBP-1、CHOP及caspase-12蛋白表达明显增加（P＜0.01）；Propofol 组大鼠海马区XBP-1、CHOP 及 caspase-12蛋白表达较 Intralipid 组减少（P＜0.01），GRP78表达增加（P＜0.01）。结论丙泊酚预处理可以减轻复苏后脑损伤，其机制可能与抑制过度的内质网应激有关。

Objective To explore the effect of propofol pretreatment on postresuscitation brain protection in a rat model of cardiac arrest and the relationship with endoplasmic reticulum stress（ERS）. Methods Forty-five male SD rats were randomly divided into Sham group（n=15）, Intralipid group （n=15）and Propofol group（n=15）. Rats of Sham group conducted all operations without induce of cardiac arrest. Rats of Intralipid group and Propofol group were operated to induce cardiac arrest by transcutaneous electrical stimulation to epicardium. In Propofol group, propofol（10 mg/kg）was adminis- trated via the intraperitoneal 30 min before operation. In Intralipid group, MCT/LCT（same volume of propofol）was administrated via the intraperitoneal 30 min before operation. The survival rats were ob-served 24 h after restoration of spontaneous circulation（ROSC）and neurological status was evaluated by neurological deficit score（NDS）. 24 h after ROSC, brains were removed for analysis of hematoxylin-eo-sin（HE）staining, TUNEL assays and western-blot. Results Compared with the Sham group, the rats in Intralipid group and Propofol group have poorer neurological outcomes（P〈0.05）, varying degrees histopathological changes in the CA1 region of the hippocampus and higher apoptosis index（P〈0.01）. Compared with the Intralipid group, there was a significant improvement in NDS（P〈0.05）, histopatho-logical changes and apoptosis index（P〈0.01）in Propofol group. The expressive protein of GRP78, XBP-1, CHOP and caspase12 in Intralipid group and Propofol group were higher than those in Sham group（P〈 0.01）. Compared with the Intralipid group, the Propofol group had lower expressive protein of XBP-1, CHOP and caspase12（P〈0.01）, but higher expression of GRP78 protein（P〈0.01）. Con-clusion Propofol pretreatment can mitigate brain injury after ROSC through inhibition of ERS.