Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., 11527 Goudi, Athens, Greece.
Mol Cell Biochem. 2011 Jul;353(1-2):235-41. doi: 10.1007/s11010-011-0791-8. Epub 2011 Mar 26.
We have previously shown that acute thyroid hormone treatment could limit reperfusion injury and increase post-ischemic recovery of function. In the present study, we further explore potential initiating mechanisms of this response. Thus, isolated rat hearts were subjected to 30 min zero-flow global ischemia (I) followed by 60-min reperfusion (R). Reperfusion injury was assessed by post-ischemic recovery of left ventricular developed pressure (LVDP%) and LDH release. T3 at a dose of 60 nM which had no effect on contractile function of non-ischemic myocardium, significantly increased LVDP% [48% (2.9) vs. 30.2% (3.3) for untreated group, P < 0.05] and reduced LDH release [8.3 (0.3) vs. 10 (0.42) for untreated group, P < 0.05] when administered at R. T4 (60 and 400 nM) had no effect on contractile function either in non-ischemic or ischemic myocardium. Administration of debutyl-dronedarone (DBD), a TRα1 antagonist abolished the T3-limiting effect on reperfusion injury: Thus, co-administration of T3 and DBD resulted in significantly lower LVDP%, [23% (4.7) vs. 48% (2.9) for T3 group, P < 0.05] and higher LDH release [9.9 (0.3) vs. 8.3 (0.3), for T3 group, P < 0.05]. In conclusion, acute T3 and not T4 treatment will be able to protect against reperfusion injury. T3 can exert this beneficial effect on ischemic myocardium at a dose that has no effects on non-ischemic myocardium. Acute T3-limiting effect on reperfusion injury is mediated, at least in part, via TRα1 receptor.
我们之前已经证明，急性甲状腺激素治疗可以限制再灌注损伤并增加缺血后功能的恢复。在本研究中，我们进一步探讨了这种反应的潜在起始机制。因此，将分离的大鼠心脏置于 30 分钟零流量全缺血（I）后进行 60 分钟再灌注（R）。通过缺血后左心室发展压（LVDP%）和 LDH 释放的恢复来评估再灌注损伤。T3 的剂量为 60 nM，对非缺血心肌的收缩功能没有影响，当在 R 时给予时，显著增加了 LVDP%[48%（2.9）比未治疗组 30.2%（3.3），P<0.05]并降低了 LDH 释放[8.3（0.3）比未治疗组 10（0.42），P<0.05]。T4（60 和 400 nM）对非缺血或缺血心肌的收缩功能均无影响。给予甲状腺激素受体α1 拮抗剂 debutyldronedarone（DBD）可消除 T3 对再灌注损伤的限制作用：因此，T3 和 DBD 的联合给药导致 LVDP%显著降低[23%（4.7）比 T3 组 48%（2.9），P<0.05]和 LDH 释放增加[9.9（0.3）比 T3 组 8.3（0.3），P<0.05]。总之，急性 T3 而非 T4 治疗将能够预防再灌注损伤。T3 可以以对非缺血心肌没有影响的剂量对缺血心肌产生这种有益作用。急性 T3 对再灌注损伤的限制作用至少部分是通过 TRα1 受体介导的。
