氢吗啡酮后处理经PI3K/Akt通路减轻大鼠心肌缺血-再灌注细胞凋亡

目的:探讨PI3K/Akt信号通路在氢吗啡酮后处理减轻大鼠心肌缺血-再灌注细胞凋亡中的作用。方法:健康雄性SD大鼠40只，按照随机数表法随机分为5组，每组8只，假手术组（Sham组）、缺血-再灌注组（I/R组）、缺血-再灌注+氢吗啡酮组（I/R+H组）、缺血-再灌注+PI3K抑制剂组（I/R+W组）、缺血-再灌注+氢吗啡酮+ PI3K抑制剂组（I/R+ H+ W组）。采用左冠状动脉前降支结扎30 min、再灌注120 min的方法建立心肌缺血-再灌注损伤模型。实验结束后，用TTC染色法测心肌梗死面积；用比色法检测血清乳酸脱氢酶（LDH）漏出量；末端标记法（TUNEL）测心肌细胞凋亡；Western blot法检测p-Akt、Bcl-2、Bax蛋白表达。采用SPSS 13.0软件行统计分析。采用单因素方差分析进行组间比较。结果:与Sham组比较，I/R组心肌梗死面积、血清LDH漏出量及心肌细胞凋亡增多，p-Akt表达和Bax表达上调，Bcl-2表达下调（ P<0.05）；与I/R组比较，I/R+H组心肌梗死面积、血清LDH漏出量及心肌细胞凋亡减少，心肌p-Akt及Bcl-2表达上调，Bax表达下调（ P<0.05）；与I/R+H组比较，I/R+H+W组心肌梗死面积、血清LDH漏出量及心肌细胞凋亡增多，p-Akt表达和Bcl-2表达下调，Bax表达上调（ P<0.05）。 结论:氢吗啡酮后处理可减轻心肌缺血-再灌注引起的心肌细胞凋亡，其心肌保护机制可能与激活PI3K/Akt信号通路有关。

Hydromorphone postconditioning attenuates myocardial ischemia/reperfusion-induced apoptosis in rats through PI3K/AKT pathway

Objective:To investigate the role of PI3K/Akt signaling pathway in hydromorphone postconditioning on alleviating myocardial ischemia/reperfusion (I/R)-induced apoptosis in rats.Methods:Forty healthy male SD rats were randomly(random number) divided into five groups, with 8 rats in each group:①sham group;②I/R group;③I/R+hydromorphone group (I/R+H group);④I/R+PI3K inhibitor group (I/R+W group); and⑤I/R+hydromorphone+PI3K inhibitor group (I/R+H+W group). The myocardial ischemia/reperfusion injury model was established by ligating the left anterior descending coronary artery for 30 min and reperfusion for 120 min. After the experiment, the area of myocardial infarction was measured by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining. The amount of serum lactate dehydrogenase (LDH) leakage was estimated by colorimetry . The cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay. The protein expressions of p-Akt, Bcl-2 and Bax were detected by Western blot. Comparisons among groups were carried out by analysis of variance (ANOVA).Results:Compared with the sham group, the area of myocardial infarction, serum LDH leakage and cardiomyocyte apoptosis were significantly increased, p-Akt and Bax expression were upregulated, Bcl-2 expression was downregulated in the I/R group ( P<0.05). Compared with the I/R group, the area of myocardial infarction, serum LDH leakage and cardiomyocyte apoptosis were markedly decreased, p-Akt and Bcl-2 expression were upregulated and Bax expression was downregulated in the I/R+H group ( P<0.05). Compared with the I/R+H group, the area of myocardial infarction, serum LDH leakage and cardiomyocyte apoptosis were significantly increased, p-Akt and Bcl-2 expression were downregulated, and Bax expression was upregulated in the I/R+H+W group ( P<0.05). Conclusions:Hydromorphone postconditioning can alleviate cardiomyocyte apoptosis induced by myocardial ischemia/reperfusion, and its protection mechanism may be related to the activation of PI3K/Akt signaling pathway.