Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore.
Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore.
复制标题
DOI：
10.1016/j.cardiores.2007.04.022
复制
发表时间：
2007-08-01
影响因子：
10.8
通讯作者：
Yellon, Derek M.
中科院分区：
文献类型：
--
作者：
Lim, Shiang Y.;Davidson, Sean M.;Hausenloy, Derek J.;Yellon, Derek M.
心肌再灌注时线粒体通透性转换孔（mPTP）的开放是细胞死亡的关键决定因素。新的研究表明，抑制mPTP开放可能是缺血预处理（IPC）和后处理（IPost）引起的心脏保护作用的基础。为了进一步评估mPTP在心脏保护中的作用，我们假设mPTP的关键成分亲环素-D（CYP-D-/-）缺乏的心脏对缺血和药物预处理和后处理所赋予的心脏保护具有抗性。对雄性/雌性野生型或CYP-D-/-小鼠进行30分钟的缺血和120分钟的再灌注。在经受体内心肌缺血-再灌注损伤的野生型小鼠中，用以下处理观察到心肌梗死面积显著减小（n ≥ 6/组; P < 0.05）：（1）IPC（28±4% vs.对照组46.2±4%）;（2）二氮嗪（5 mg/kg）预处理（26.4±3%对比溶剂对照中的54±10%）;（3）IPost-1或IPost-2，3或6个10秒循环的缺血-再灌注（分别为27.2±3%和32± 4%，对照组为46.2±4%）;（40微克/千克）（28.3±1% vs.溶剂对照组48±4%）;（5）环孢菌素-A（10 mg/kg）（32.3± 3%对载体对照中的48 ± 4%）。然而，有趣的是，在使用相同治疗方案的CYP-D-/-小鼠中未证实梗死限制效应：（对照组27.9±5%对比IPC组31.2±7%，IPost-1组30.2±5%，IPost-2组24.7±8%;溶媒对照组30.1±4%对比二氮嗪组26.4±7%;溶剂对照组为24.6±4%，缓激肽组为24.9±5%，环孢菌素A组为26.8±7%，桑利福菌素A组为32.5±6%：n ≥ 6/组：P > 0.05）。这项研究表明，mPTP在缺血和药物预处理和后处理引起的心脏保护中起着关键作用。
The opening of the mitochondrial permeability transition pore (mPTP) at the time of myocardial reperfusion is a critical determinant of cell death. Emerging studies suggest that suppression of mPTP opening may underlie the cardioprotection elicited by both ischemic preconditioning (IPC) and postconditioning (IPost). To further evaluate the role of the mPTP in cardioprotection, we hypothesized that hearts deficient in cyclophilin-D (CYP-D-/-), a key component of the mPTP, will be resistant to cardioprotection conferred by ischemic and pharmacological preconditioning and postconditioning. Male/female wild type or CYP-D-/- mice were subjected to 30 min of ischemia and 120 min of reperfusion. In wild type mice subjected to in vivo myocardial ischemia-reperfusion injury, a significant reduction in myocardial infarct size was observed with the following treatments (n ≥ 6/group; P < 0.05): (1) IPC (28±4% vs. 46.2±4% in control); (2) Diazoxide (5 mg/kg) pre-treatment (26.4±3% vs. 54±10% in vehicle control); (3) IPost-1 or IPost-2, three or six 10-s cycles of ischemia-reperfusion (27.2±3% and 32±4%, respectively vs. 46.2±4% in control); (4) Bradykinin (40 μg/kg) (28.3±1% vs. 48±4% in vehicle control); (5) cyclosporin-A (10 mg/kg) (32.3±3% vs. 48±4% in vehicle control) (6) sanglifehrin-A (25 mg/kg) (29.3±3% vs. 48±4% in vehicle control). Interestingly, however, no infarct-limiting effects were demonstrated in CYP-D-/- mice with the same treatment protocols: (27.9±5% in control vs. 31.2±7% with IPC, 30.2±5% with IPost-1, 24.7±8% with IPost-2; 30.1±4% in vehicle control vs. 26.4±7% with diazoxide; 24.6±4% in vehicle control vs. 24.9±5% with bradykinin, 26.8±7% with cyclosporin-A, 32.5±6% with sanglifehrin-A: n ≥ 6/group: P > 0.05). This study demonstrates that the mPTP plays a critical role in the cardioprotection elicited by ischemic and pharmacological preconditioning and postconditioning.
登录
查看更多内容
影响因子：
4.8
作者：
Costa, Alexandre D. T.;Jakob, Regina;Garlid, Keith D.
通讯作者：
Garlid, Keith D.
影响因子：
64.8
作者：
Nakagawa, T;Shimizu, S;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
影响因子：
37.8
作者：
MURRY, CE;JENNINGS, RB;REIMER, KA
通讯作者：
REIMER, KA
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
37.8
作者：
Hausenloy, D;Wynne, A;Yellon, D
通讯作者：
Yellon, D