Schultz J E, Hsu A K, Barbieri J T, Li P L, Gross G J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Physiol. 1998 Aug;275(2):H495-500. doi: 10.1152/ajpheart.1998.275.2.H495.
It has been previously demonstrated that Gi/o proteins are involved in ischemic preconditioning (IPC) in rabbits and dogs; however, there has been controversy as to the role of Gi/o proteins in IPC in in vivo rat infarct models. Therefore, the role of G proteins in the cardioprotective effect of IPC in a rat infarct model was reevaluated. Cardioprotection as indicated by infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by triphenyltetrazolium stain. The control group, which was subjected to 30 min of occlusion (Occ) and 2 h of reperfusion (Rep), had an IS/AAR of 46 +/- 6%. A single 5-min Occ followed by 10 min of Rep (1x PC) as well as three 5-min Occ periods interspersed with 5 min of Rep (3x PC) markedly reduced IS/AAR (6 +/- 1 and 8 +/- 1%, respectively). Pretreatment with pertussis toxin (10 microg/kg ip) for 48 h before 1x PC or 3x PC completely abolished their cardioprotective effects (46 +/- 5 and 38 +/- 4%, respectively). Pertussis toxin had no effect on IS/AAR and did not inactivate Gi/o proteins as assessed by an in vitro ADP-ribosylation assay of heart homogenates. These results demonstrate that the cardioprotective effect of IPC is mediated by a small subpopulation of Gi/o proteins in the intact rat heart.
先前已证明，Gi/o蛋白参与家兔和犬的缺血预处理（IPC）；然而，在体内大鼠梗死模型中，Gi/o蛋白在IPC中的作用一直存在争议。因此，重新评估了G蛋白在大鼠梗死模型中IPC心脏保护作用中的作用。通过三苯基四氮唑染色确定梗死面积（IS）占危险区域面积（IS/AAR）百分比所表明的心脏保护作用。对照组经历30分钟的闭塞（Occ）和2小时的再灌注（Rep），其IS/AAR为46±6%。单次5分钟的Occ随后10分钟的Rep（1次PC）以及三次5分钟的Occ期间穿插5分钟的Rep（3次PC）显著降低了IS/AAR（分别为6±1%和8±1%）。在1次PC或3次PC之前48小时腹腔注射百日咳毒素（10μg/kg）预处理完全消除了它们的心脏保护作用（分别为46±5%和38±4%）。百日咳毒素对IS/AAR没有影响，并且通过心脏匀浆的体外ADP-核糖基化测定评估，它不会使Gi/o蛋白失活。这些结果表明，IPC的心脏保护作用是由完整大鼠心脏中一小部分Gi/o蛋白介导的。
