摘要
目的探讨PI3K/Akt信号通路在舒芬太尼后处理减轻在体大鼠心肌缺血-再灌注损伤时细胞凋亡中的作用。方法取90只健康成年雄性SD大鼠,采用随机数字表法分为五组:假手术组(Sham组),只穿线不结扎;缺血-再灌注组(IR组),结扎左冠状动脉前降支造成心肌缺血30min,再灌注120 min;舒芬太尼后处理组(Sufen组),在灌注即刻,给予舒芬太尼1.0μg/kg输注3min,再灌注处理同IR组;舒芬太尼后处理^+LY294002(PI3K抑制剂)组(SL组),再灌注前10min给予LY294002 0.3mg/kg,并行舒芬太尼后处理;LY294002组(IL组),再灌注前10 min给予LY294002 0.3mg/kg,再灌注120min。在缺血前即刻(T_0)、缺血30min(T_1)、再灌注60min(T_2)和再灌注120min(T_3)时记录HR和MAP;再灌注末,测定心肌梗死面积(IS/AAR);再灌注15 min时,采用Western blot法测定心肌组织总的Akt和磷酸化的Akt蛋白含量;在再灌注末,用RT_-PCR检测Bax和Bcl-2mRNA的表达。结果五组大鼠组间组内HR差异无统计学意义;T_2、T_3时IR组、SL组和IL组MAP明显低于Sham组(P<0.05);Sufen组IS/AAR明显低于IR、SL和IL组(P<0.05);五组心肌总的Akt蛋白含量表达差异无统计学意义;与Sufen组比较,sham、IR、SL和IL组磷酸化的Akt表达明显下调(P<0.05),IR组、SL和IL组Bax mRNA的表达明显升高,Bcl-2mRAN的表达明显降低(P<0.05)。结论舒芬太尼后处理可减轻心肌缺血-再灌注损伤,可能与激活PI3K/Akt信号通路,降低Bax和增加Bcl-2蛋白表达而达到抑制心肌细胞的凋亡有关。
Objective To investigate the effect of sufentanil postconditioning on myocardial ischemia-reperfusion injury in rats in vivo and the role of PI3K/Akt signaling pathway.Methods Ninety healthy male SD rats were randomly allocated to Sham group（the coronary suture was passed,not tied,and maintained for 150min）,group IR（ischemia for 30 min followed by 120 min reperfusion）,group Sufen（administration of 1 μg/kg sufentanil for 3 min at the onset of reperfusion following 30 min of ischemia）,group SL（administration of sufentanil and 0.3 mg/kg LY294002DMSO）for 10 min prior to reperfusion）and group IL（only administration 0.3mg/kg LY294002 for 10 min prior to reperfusion）.HR and MAP were measured at the following time points：end of stabilization prior to ischemia（baseline）;30min of ischemia;60and 120 min of reperfusion;at the end of 120 min reperfusion,the rats were sacrificed for assessment infarct area,the expression of Bax and Bcl-2 mRNA;the myocardial tissue samples were collected 15 min following reperfusion to determine the total and phosphorylated Akt expression by Western blot.Results There were no significant differences in the HR among the 6 groups;MAP were significantly decreased at 60 and 120 min following reperfusion（P〈0.05）in group IR,groups SL and IL compared to group Sham;there were no significant differences in the total Akt expression among the 6groups;phosphorylated Akt were significantly upregulated,the infarct area were significantly decreased,Bax mRNA levels were significantly decreased and Bcl-2mRNA levels were significantly increased（P〈0.05）in group Sufen compared to group IR,there were no significant differences respectively between groups SL,IL and IR.Conclusion Sufentanil postconditioning can induce myocardial protection through activation of the PI3K/Akt signaling pathway and inhibition of cell apoptosis via down-regulation Bax and up-regulation Bcl-2expression.
出处
《临床麻醉学杂志》
CAS
CSCD
北大核心
2016年第11期1116-1119,共4页
Journal of Clinical Anesthesiology
基金
沈阳市科学技术项目计划(F13-221-9-71)
关键词
舒芬太尼后处理
心肌缺血-再灌注损伤
PI3K/AKT
Sufentanil postconditioning
Myocardial ischemia-reperfusion injury
Phosphatidylinositol-3-kinase/protein-serine-threonine kinases
