Hepatobiliary pancreatic surgery, China-Japan Union Hospital of Jilin University, 126 XianTaiStreet, Changchun, 130033, China.
Vascular surgery, China-Japan Union Hospital of Jilin University, 126 XianTai Street, Changchun, 130033, China.
Sci Rep. 2018 Jul 19;8(1):10941. doi: 10.1038/s41598-018-29196-x.
The present study was aimed to explore the role of endothelins in remote preconditioning (RP)-induced myocardial protection in ischemia-reperfusion (IR) injury. RP stimulus was given by subjecting hind limb to four cycles of ischemia and reperfuion (5 minutes each) using blood pressure cuff in male rats. Following RP, hearts were isolated and subjected to 30 minutes of ischemia and 120 minutes of reperfusion on Langendorff apparatus. The extent of myocardial injury was determined by measuring the levels of LDH-1, CK-MB and cardiac troponin T (cTnT) in coronary effluent; caspase-3 activity and Bcl 2 expression in heart (apoptosis); infarct size by triphenyl tetrazolium chloride and contractility parameters including left ventricular developed pressure, dp/dt dp/dt and heart rate. RP reduced ischemia reperfusion-induced myocardial injury, increased the levels of endothelin 1 (in blood), Akt-P, GSK-3β-P and P-connexin 43 (in hearts). Pretreatment with ET receptor antagonist, BQ 123 (1 and 2 mg/kg), ET receptor antagonist, BQ 788 (1 and 3 mg/kg) and dual inhibitor of ET and ET receptor, bonsentan (25 and 50 mg/kg) abolished these effects of RP. However, the effects of bonsentan were more pronounced in comparison to BQ 123 and BQ 788. It is concluded that RP stimulus may release endothelin 1 in the blood, which may activate myocardial ET and ET receptors to trigger cardioprotection through connexin 43 and Akt/GSK-3β pathway.
本研究旨在探讨内皮素在远程预处理（RP）诱导的缺血再灌注（IR）损伤心肌保护中的作用。雄性大鼠使用血压袖带对后肢进行 4 个周期的缺血再灌注（每个 5 分钟），作为 RP 刺激。在 RP 后，将心脏在 Langendorff 仪器上进行 30 分钟的缺血和 120 分钟的再灌注。通过测量冠状动脉流出液中的 LDH-1、CK-MB 和心肌肌钙蛋白 T（cTnT）水平来确定心肌损伤程度；心脏中的 caspase-3 活性和 Bcl-2 表达（凋亡）；氯化三苯基四氮唑和收缩性参数（包括左心室发展压、dp/dt dp/dt 和心率）测定梗死面积。RP 减少了缺血再灌注引起的心肌损伤，增加了内皮素 1（血液中的）、Akt-P、GSK-3β-P 和 P-连接蛋白 43（心脏中的）水平。用内皮素受体拮抗剂 BQ 123（1 和 2mg/kg）、内皮素受体拮抗剂 BQ 788（1 和 3mg/kg）和内皮素和内皮素受体双重抑制剂 boncentan（25 和 50mg/kg）预处理可消除 RP 的这些作用。然而，与 BQ 123 和 BQ 788 相比，bonsentan 的作用更为明显。结论是 RP 刺激可能会在血液中释放内皮素 1，内皮素 1 可能通过连接蛋白 43 和 Akt/GSK-3β 途径激活心肌 ET 和 ET 受体，从而触发心肌保护作用。
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