远程缺血预处理通过甘氨酸受体激活提供体液交叉种属心脏保护。

Remote ischemic conditioning provides humoural cross-species cardioprotection through glycine receptor activation.

机构信息

Cardiovascular Diseases Research Group, Department of Cardiology, Vall d'Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Pg Vall d'Hebron 119-129, 08035 Barcelona, Spain.

出版信息

Cardiovasc Res. 2017 Jan;113(1):52-60. doi: 10.1093/cvr/cvw242.

DOI:10.1093/cvr/cvw242

PMID:28069702

Abstract

AIMS

Remote ischaemic conditioning (RIC) releases a humoural factor able to exert cross-species cardioprotection when plasma dialysate is applied to isolated hearts. However, the exact chemical nature of this factor is currently unknown.

METHODS AND RESULTS

RIC (4 × 5min femoral occlusion/5min reperfusion) was applied to 10 male pigs, and blood was taken before and after the manoeuvre. Discriminant analysis of H-NMR spectra (n = 10-12) obtained from plasma dialysates (12-14 kDa cut-off) allowed to demonstrate a different metabolic profile between control and postRIC samples, with lactate (2.671 ± 0.294 vs. 3.666 ± 0.291 μmol/mL, P = 0.020), succinate (0.062 ± 0.005 vs. 0.082 ± 0.008 μmol/mL, P = 0.035) and glycine (0.055 ± 0.009 vs. 0.471 ± 0.151 μmol/mL, P = 0.015) being the main responsible for such differences. Plasma dialysates were then given to isolated mice hearts submitted to global ischaemia (35 min) and reperfusion (60 min), for 30 min before ischaemia or during the first 15 min of reflow. Infarct size was significantly reduced when postRIC dialysate was applied before ischaemia as compared with hearts pretreated with control dialysate (44.81 ± 3.22 vs. 55.55 ± 2.53%, P = 0.012, n = 12). Blockade of glycine receptors with strychnine 10 μM inhibited the protective effect caused by pretreatment with postRIC dialysate (52.76 ± 6.94 vs. 51.92 ± 5.78%, P-NS, n = 5), whereas pretreatment with glycine 3 mmol/L, but not succinate 100 μmol/L, mimicked RIC protection (41.90 ± 4.50% in glycine-treated vs. 61.51 ± 5.16 and 64.73 ± 4.47% in succinate-treated and control hearts, respectively, P < 0.05, n = 4-7).

CONCLUSIONS

RIC releases glycine and exerts cross-species cardioprotection against infarction through glycine receptor activation.

摘要

目的

远程缺血预处理（RIC）释放出一种体液因子，当将其血浆透析液应用于分离的心脏时，能够发挥跨物种的心脏保护作用。然而，这种因子的确切化学性质目前尚不清楚。

方法和结果

对 10 头雄性猪进行 RIC（4×5 分钟股动脉闭塞/5 分钟再灌注）处理，并在操作前后采集血液。对来自血浆透析液（12-14 kDa 截止）的 H-NMR 光谱（n=10-12）进行判别分析，结果表明对照和 postRIC 样本之间存在不同的代谢谱，其中乳酸（2.671±0.294 与 3.666±0.291 μmol/mL，P=0.020）、琥珀酸（0.062±0.005 与 0.082±0.008 μmol/mL，P=0.035）和甘氨酸（0.055±0.009 与 0.471±0.151 μmol/mL，P=0.015）是造成这种差异的主要原因。然后将血浆透析液给予接受全脑缺血（35 分钟）和再灌注（60 分钟）的分离小鼠心脏，在缺血前 30 分钟或再灌注的前 15 分钟给予。与用对照透析液预处理的心脏相比，在用预处理的 postRIC 透析液预处理后再进行缺血时，梗塞面积明显减小（44.81±3.22 与 55.55±2.53%，P=0.012，n=12）。用 10 μM 士的宁阻断甘氨酸受体抑制了用 postRIC 透析液预处理引起的保护作用（52.76±6.94 与 51.92±5.78%，P-NS，n=5），而用 3 mmol/L 的甘氨酸预处理，但不是用 100 μmol/L 的琥珀酸预处理，模拟了 RIC 的保护作用（在甘氨酸处理的心脏中为 41.90±4.50%，而在琥珀酸处理的和对照的心脏中分别为 61.51±5.16%和 64.73±4.47%，P<0.05，n=4-7）。