Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Biosci Rep. 2018 Oct 17;38(5). doi: 10.1042/BSR20181315. Print 2018 Oct 31.
The present study was designed to determine whether glycogen synthase kinase-3β (GSK-3β) was involved in the cardioprotection by α7 nicotinic acetylcholine receptor (α7nAChR) agonist and limb remote ischemic postconditionings. Forty male Sprague-Dawley rats were randomly divided equally into control (C), α7nAChR agonist postconditioning (P), limb remote ischemic postconditioning (L), combined α7nAChR agonist and limb remote ischemic postconditioning (P+L) groups. At the end of experiment, serum cTnI, creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high mobility group protein (HMGB1) and interleukin-10 (IL-10) levels were measured; infarct size (IS), myocardial expressions of GSK-3β, p-GSK-3β (Ser9), nuclear factor-κB (NF-κB) and p-NF-κB (Ser536) in the ischemic area were assessed. The results showed that compared with group C, IS, serum cTnI and CK-MB levels obviously decreased in groups P, L and P+L. Compared with groups P and L, IS, serum cTnI and CK-MB levels significantly decreased in group P+L. Compared with group C, serum TNF-α, IL-6 and HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) evidently decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in groups P, L and P+L. Compared with group P, serum TNF-α, IL-6 and HMGB1 levels and myocardial expression of p-NF-κBp65 (Ser536) significantly increased, and myocardial expression of p-GSK-3β (Ser9) evidently decreased in group L. Compared with group L, serum TNF-α, IL-6, HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) significantly decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in group P+L. In conclusion, our findings indicate that inhibition of GSK-3β to decrease NF-κB transcription is one of cardioprotective mechanisms of α7nAChR agonist and limb remote ischemic postconditionings by anti-inflammation, but improved cardioprotection by combined two interventions is not completely attributable to an enhanced anti-inflammatory mechanism.
本研究旨在探讨糖原合酶激酶-3β（GSK-3β）是否参与α7 烟碱型乙酰胆碱受体（α7nAChR）激动剂和肢体远程缺血后处理的心脏保护作用。40 只雄性 Sprague-Dawley 大鼠随机均分为对照组（C）、α7nAChR 激动剂后处理组（P）、肢体远程缺血后处理组（L）和联合α7nAChR 激动剂和肢体远程缺血后处理组（P+L）。实验结束时，检测血清肌钙蛋白 I（cTnI）、肌酸激酶同工酶-MB（CK-MB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、高迁移率族蛋白 B（HMGB1）和白细胞介素-10（IL-10）水平；评估缺血区的糖原合酶激酶-3β（GSK-3β）、磷酸化糖原合酶激酶-3β（p-GSK-3β，Ser9）、核因子-κB（NF-κB）和磷酸化核因子-κB（p-NF-κB，Ser536）的表达；计算心肌梗死面积（IS）。结果显示，与 C 组相比，P、L 和 P+L 组的 IS、血清 cTnI 和 CK-MB 水平明显降低。与 P 和 L 组相比，P+L 组的 IS、血清 cTnI 和 CK-MB 水平显著降低。与 C 组相比，P、L 和 P+L 组的血清 TNF-α、IL-6 和 HMGB1 水平以及心肌 p-NF-κBp65（Ser536）的表达明显降低，p-GSK-3β（Ser9）的表达明显升高。与 P 组相比，L 组的血清 TNF-α、IL-6 和 HMGB1 水平以及心肌 p-NF-κBp65（Ser536）的表达显著升高，p-GSK-3β（Ser9）的表达明显降低。与 L 组相比，P+L 组的血清 TNF-α、IL-6、HMGB1 水平以及心肌 p-NF-κBp65（Ser536）的表达显著降低，p-GSK-3β（Ser9）的表达明显升高。结论：本研究表明，抑制 GSK-3β 减少 NF-κB 转录是α7nAChR 激动剂和肢体远程缺血后处理通过抗炎发挥心脏保护作用的机制之一，但两种干预措施联合应用增强的心脏保护作用不完全归因于增强的抗炎机制。
