Department of Cardiology, General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China.
Mol Med Rep. 2013 Aug;8(2):696-702. doi: 10.3892/mmr.2013.1544. Epub 2013 Jun 25.
The aim of the present study was to investigate whether a gradually increasing reperfusion algorithm, in which the brief reperfusion was lengthened as the duration of each reperfusion/reocclusion cycle remained fixed, enhances cardioprotection. Rats were randomized into 5 groups: the sham, reperfusion injury (R/I), gradually decreased reperfusion (GDR; 30/10‑25/15‑15/25‑10/30 sec of reperfusion/reocclusion), equal reperfusion (ER; 4 20/20‑sec reperfusion/reocclusion cycles) and gradually increased reperfusion (GIR; 10/30‑15/25‑25/15‑30/10 sec of reperfusion/reocclusion). The rats were sacrificed to measure serum markers, apoptotic indices and infarct size. Western blot analyses were used to analyze the expression of molecules involved in important signaling pathways. All the three postconditioning patterns were found to provide cardioprotection (P<0.05 compared with the R/I group). GIR provided optimum cardioprotection, followed by ER and then GDR. Apoptotic index and serum marker levels were significantly reduced in the GIR compared with the ER group (P<0.05). The enhanced cardioprotection provided by GIR was accompanied by significantly increased levels of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and Bcl‑2, as well as lower levels of p38/c‑Jun N‑terminal kinase (JNK) phosphorylation, tumor necrosis factor α (TNFα), caspase‑8, Bax, caspase‑9 and cytochrome c (Cyt‑c) in the cytoplasm of rats (P<0.05, all compared with ER). The infarct size in the rats of the GIR group was also smaller compared with that in the rats of the ER group, but this difference was not significant (16.30±5.22 vs. 20.57±6.32%, P>0.05). All the variables measured in the present study were significantly improved in the GIR group compared with the GDR group (P<0.05). In conclusion, the association between brief reperfusion and reocclusion is an important factor in postconditioning algorithms. Additionally, GIR results in improved cardioprotection compared with that achieved by the remaining algorithms examined.
本研究旨在探讨逐渐增加再灌注算法（即每次再灌注/再闭塞循环中短暂再灌注时间逐渐延长）是否能增强心脏保护作用。大鼠随机分为 5 组：假手术组、再灌注损伤组（R/I）、逐渐减少再灌注组（GDR；30/10-25/15-15/25-10/30 秒再灌注/再闭塞）、等时再灌注组（ER；4 个 20/20 秒再灌注/再闭塞循环）和逐渐增加再灌注组（GIR；10/30-15/25-25/15-30/10 秒再灌注/再闭塞）。处死大鼠以测量血清标志物、细胞凋亡指数和梗死面积。Western blot 分析用于分析参与重要信号通路的分子的表达。所有三种后处理模式均提供心脏保护作用（与 R/I 组相比，P<0.05）。GIR 提供最佳的心脏保护作用，其次是 ER，然后是 GDR。与 ER 组相比，GIR 组的细胞凋亡指数和血清标志物水平显著降低（P<0.05）。GIR 提供的增强心脏保护作用伴随着细胞外信号调节激酶 1/2（ERK1/2）磷酸化和 Bcl-2 的显著增加，以及 p38/c-Jun N-末端激酶（JNK）磷酸化、肿瘤坏死因子 α（TNFα）、半胱天冬酶-8、Bax、半胱天冬酶-9 和细胞质中的细胞色素 c（Cyt-c）水平降低（与 ER 相比，所有 P<0.05）。与 ER 组相比，GIR 组大鼠的梗死面积也较小，但差异无统计学意义（16.30±5.22%比 20.57±6.32%，P>0.05）。与 GDR 组相比，GIR 组所有测量变量均显著改善（P<0.05）。总之，短暂再灌注与再闭塞之间的关联是后处理算法中的一个重要因素。此外，与其余 3 种算法相比，GIR 可获得更好的心脏保护作用。
