丙泊酚后处理对离体大鼠缺血再灌注心肌的保护作用及机制

目的研究丙泊酚后处理对离体大鼠缺血再灌注心肌细胞的保护作用以及对PI3K/Akt信号通路的影响。方法选用SD大鼠28只,按照随机数字表法分为缺血再灌注组(I/R组)、丙泊酚后处理组(PPC组)、丙泊酚后处理+Wortmannin后处理组(PPC+W组)、Wortmannin组(W组)。4组均建立Langendorff离体心肌缺血再灌注模型。各组心肌做相应分组处理后,观察缺血前及再灌注120 min时左室心功能变化情况,免疫组化检测Bcl-2蛋白的表达,Tunel法检测各组心肌细胞凋亡情况,Western blot测定p-Akt(Ser473)蛋白表达。结果与I/R组相比,PPC组LVEDP降低(43.31±4.70)vs(29.93±3.72),P<0.05],+dp/dtmax和-dp/dtmax均明显升高(1 140±138)vs(1 622±160),(749±99)vs(1 008±178),P<0.05],心肌组织Bcl-2蛋白和p-Akt的表达均增加(0.171 9±0.012 1)vs(0.199 1±0.014 4),(0.241 4±0.053 9)vs(0.436 3±0.081 7),P<0.05],心肌细胞凋亡明显减少(33.87±1.72)vs(29.84±1.83),P<0.05]。Wortmannin能阻断丙泊酚后处理的心肌保护效应(P<0.05)。结论丙泊酚后处理能减少离体大鼠缺血再灌注心肌细胞凋亡,发挥心肌保护作用,其保护机制与激活PI3K/Akt信号通路及上调Bcl-2蛋白的表达有关。

Cardioprotective effect of propofol postconditioning on myocardium against ischemiareperfusion injury in isolated rat hearts

Objective To investigate the protective effect of propofol postconditioning on myocardium against ischemia-reperfusion injury in isolated rat hearts and the role of PI3K/Akt signaling pathway.Methods Twenty-eight rats were randomly divided into four groups including an ischemia-reperfusion group(I/R group),a propofol postconditioning group(PPC group),a propofol postconditioning combined with wortmannin group(PPC+W group) and a wortmannin group(W group).The I/R models of isolated hearts were established in all of the groups.The LVEDP and dp/dtmax were measured before ischemia and at 120 min after reperfusion.The expression of Bcl-2 was measured by immunohistochemistry,the apoptotic index was measured by TUNEL,and the expression of p-Akt(Ser473) was measured by Western blotting.Results Compared with the I/R group,the LVEDP significantly decreased(43.31±4.70 vs 29.93±3.72,P<0.05),and +dp/dtmax and-dp/dtmax significantly increased in the PPC group(1 140±138 vs 1 622±160;749±99 vs 1 008±178,P<0.05).The expression of Bcl-2 and p-Akt in the myocardium of the PPC group was significantly higher than that of the I/R group(0.171 9±0.012 1 vs 0.199 1±0.014 4;0.241 4±0.053 9 vs 0.436 3±0.081 7,P<0.05),while the proportion of apoptotic cardiomyocytes decreased significantly in the PPC group as compared with the I/R group(33.87±1.72 vs 29.84±1.83,P<0.05).Wortmannin could block the protective effect of propofol postconditioning(P<0.05).Conclusion Propofol postconditioning could attenuate the apoptosis in the isolated heart induced by I/R probably through PI3K/Akt signal pathway and Bcl-2 upregulation.