摘要
目的研究心肺复苏后大鼠肝细胞损伤的机制及丙泊酚(propofol)预处理的保护作用。方法采用窒息(琥珀酰胆碱)合并0.5mol/L冰氯化钾停跳液致大鼠心脏骤停,停跳5min后开始心肺复苏。健康Sprague Dawley雄性大鼠56只,随机分7组:Con组(假手术组)、IR1组(复苏后3h组)、IR2组(复苏后6h组)、IR3组(复苏后12h组)、IR4组(复苏后24h组)、P1组(丙泊酚预处理+复苏后6h组)、P2组(丙泊酚预处理+复苏后12h组),每组8只。P组自缺血前30min静脉输注丙泊酚1mg/(kg·min),Con组及IR组按0.1mL/(kg·min)速率输注乳酸钠林格液,然后开始I/R模型制作。在相应的时间点处死大鼠,采用酶生化法测定各组大鼠血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)表达;采用免疫组化法观察各组大鼠肝细胞Bcl-2、Bax和核因子-κB(NF—κB)表达情况。结果IR组ALT和AST表达较Con组明显升高(P〈0.05),IR1组ALT和AST表达最高;与Con组比较,IR2组、IR3组和IR4组肝细胞抑凋亡蛋白Bcl-2表达明显降低(P〈0.05),IR1组、IR2组、IR3组和IR4组促凋亡蛋白Bax表达明显升高(P〈0.05),肝细胞NF—κB表达明显增加(P〈0.05);与IR组比较,P1组和P2组ALT和AST表达明显降低(P〈0.05),肝细胞抑凋亡蛋白Bcl-2表达明显增多(P〈0.05),促凋亡蛋白Bax表达明显下降(P〈0.05),肝细胞NF—κB表达也明显减少(P〈0.05)。结论心肺复苏后大鼠存在肝细胞损伤和凋亡,其中Bcl-2/Bax比例失衡、NF—κB的激活可能在肝细胞损伤中起重要作用;丙泊酚预处理可有效降低Bax的表达,增加Bcl-2的表达,从而抑制肝细胞的凋亡,发挥肝细胞保护作用。
Objective To study the influence of propofol preconditioning on hepatocyte injury in the rats after cardiopulmonary resuscitation. Methods The asphyxia (succinylcholine) combined with 0. 5 mol/L ice potassium cardioplegia induced cardiac arrest in rats, and lasted 5 rain, then started to cardiopulmonary resuscitation. 56 health Sprague Dawley male rats were divided into 7 groups: Con group (sham operation group), IR1 group (3 h after recovery), IR2 group (6 h after recovery), IR3 group (12 h after recovery) , IR4 group (24 h after recovery) , P1 group (propofol preconditioning + 6 h after recovery), P2 group (propofol preconditioning + 12 h after recovery), 8 rats in each group. Since 30 min before ischemia, P group was infused propofol by 1 mg/(kg·min), Con group and IR group was infused lactated Ringer's solution by 0.1 mL/( kg·min) rate, and then I/R models were made. At corresponding time points, rats were sacrificed, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content were measured by using enzyme biochemical determination; the expression of Bcl - 2, Bax and nuclear factor - κB ( NF - κB) by immunohistochemical method in rat liver cells. Results Compared with Con group, ALT and AST in IR group increased significantly (P 〈 0.05 ), ALT and AST expression reached the maximum in IR1 group; Compared with Con group, liver ceU apoptosis protein Bcl - 2 expression was significantly decreased in IR2 group, IR3 group and IR4 group ( P 〈 0. 05 ) ; Bax expression was significantly increased in IR1 group, IR2 group, IR3 group and IR4 group ( P 〈 0.05 ) , liver cell NF - κB expression was significantly increased ( P 〈 0.05 ) ; Compared with IR group, ALT and AST expression decreased significantly in P1 and P2 group (P 〈 0.05 ) , Bcl - 2 expression was significantly increased ( P 〈 0.05 ), Bax expression was significantly decreased ( P 〈 0. 05 ) , NF - κB expression in liver cells also dec
出处
《中国急救医学》
CAS
CSCD
北大核心
2012年第11期1009-1011,共3页
Chinese Journal of Critical Care Medicine