Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China.
Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, China.
Sci Rep. 2017 Aug 11;7(1):7922. doi: 10.1038/s41598-017-08388-x.
We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.
我们研究了内质网应激（ERS）在慢性间歇性低氧（CIHH）诱导的心脏保护中的作用。成年雄性 Sprague-Dawley 大鼠接受模拟 5000 米海拔的 CIHH 处理，每天 6 小时，共 28 天。心脏用 Langendorff 装置分离并灌注，进行 30 分钟缺血，然后再进行 60 分钟再灌注。评估心功能、梗死面积和乳酸脱氢酶（LDH）活性。通过 Western blot 分析测定 ERS 分子伴侣（GRP78、CHOP 和 caspase-12）的表达。与对照组大鼠相比，CIHH 处理可改善左心室功能的恢复，并降低 I/R 后的心脏梗死面积和 LDH 活性。此外，CIHH 处理抑制了 ERS 相关因子（包括 GRP78、CHOP 和 caspase-12）的过度表达。应用 ERS 诱导剂二硫苏糖醇和蛋白激酶 C（PKC）抑制剂 Chelerythrine 可消除 CIHH 诱导的心脏保护和 ERS 抑制。综上所述，CIHH 处理通过 PKC 信号通路抑制 ERS 发挥对 I/R 损伤的心脏保护作用。
