Zhang Yuwen, Zhang Lei, Gu Erwei, Zhu Bingqing, Zhao Xianya, Chen Jingjing
Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China
Exp Biol Med (Maywood). 2016 Mar;241(6):650-7. doi: 10.1177/1535370215622706. Epub 2016 Jan 8.
Sufentanil, a commonly used opioid analgesic, could mimic ischemia postconditioning to attenuate ischemia reperfusion injury, but this effect might be hindered in diabetic animals by inhibition of glycogen synthase kinase-3β phosphorylation. Also, diabetes can abrogate the cardioprotection of sevoflurane (an inhaled anesthetic) against ischemia reperfusion injury, and short-term insulin treatment does not restore protection by sevoflurane postconditioning. We hypothesized that long-term insulin treatment might restore the cardioprotective effect of sufentanil postconditioning in diabetic rats via phosphorylation of glycogen synthase kinase-3β. Streptozotocin (55 mg/kg)-induced diabetic rats received insulin (Novolin N, 6-8 u/d) for two days or two weeks, then were exposed to 30-min ischemia and 120-min reperfusion. Sufentanil postconditioning was performed 5 min before the onset of reperfusion. Controls included non-diabetic rats, sham surgery for ischemia/reperfusion, and sufentanil vehicle. Infarct size, cardiac troponin I, and phosphorylated glycogen synthase kinase-3β were examined. Sufentanil postconditioning reduced infarct size by 46% in non-diabetic rats (P < 0.001), but diabetes prevented this protective effect. Two-day insulin treatment was not effective, but two-week treatment reduced infarct size by 45% (P < 0.001), reduced cardiac troponin I by 33% (P < 0.001), and increased phosphorylated glycogen synthase kinase-3β levels (P < 0.001) in the diabetic sufentanil postconditioning group. In conclusion, sufentanil-induced cardioprotection was restored by long-term insulin treatment. The underlying mechanism may be increased phosphorylation of glycogen synthase kinase-3β.
舒芬太尼是一种常用的阿片类镇痛药，它可以模拟缺血后处理以减轻缺血再灌注损伤，但在糖尿病动物中，这种作用可能会因糖原合酶激酶-3β磷酸化受到抑制而受阻。此外，糖尿病会消除七氟烷（一种吸入性麻醉剂）对缺血再灌注损伤的心脏保护作用，短期胰岛素治疗并不能恢复七氟烷后处理的保护作用。我们推测，长期胰岛素治疗可能通过糖原合酶激酶-3β的磷酸化来恢复舒芬太尼后处理对糖尿病大鼠的心脏保护作用。链脲佐菌素（55 mg/kg）诱导的糖尿病大鼠接受胰岛素（诺和灵N，6 - 8 u/d）治疗两天或两周，然后经历30分钟的缺血和120分钟的再灌注。在再灌注开始前5分钟进行舒芬太尼后处理。对照组包括非糖尿病大鼠、缺血/再灌注假手术组和舒芬太尼溶剂对照组。检测梗死面积、心肌肌钙蛋白I和磷酸化糖原合酶激酶-3β。舒芬太尼后处理使非糖尿病大鼠的梗死面积减少了46%（P < 0.001），但糖尿病阻止了这种保护作用。两天的胰岛素治疗无效，但两周的治疗使糖尿病舒芬太尼后处理组的梗死面积减少了45%（P < 0.001），心肌肌钙蛋白I降低了33%（P < 0.001），并增加了磷酸化糖原合酶激酶-3β水平（P < 0.001）。总之，长期胰岛素治疗恢复了舒芬太尼诱导的心脏保护作用。其潜在机制可能是糖原合酶激酶-3β磷酸化增加。
