摘要
目的探讨丝裂素活化蛋白激酶家系（ＭＡＰＫｓ）在大鼠心脏缺血预处理（ＩＰＣ）保护中的作用。方法在离体灌注的ＳＤ大鼠心脏缺血／再灌注（Ｉ／Ｒ）模型上，观察ＩＰＣ对于Ｉ／Ｒ后损伤的影响，并观察ＭＡＰＫｓ中三种激酶［细胞外信号调节激酶（ＥＲＫｓ）、蛋白激酶ｐ３８（ｐ３８）、应激活化蛋白激酶（ＳＡＰＫ）］活性的变化及其与保护作用的关系。结果ＩＰＣ明显改善大鼠Ｉ／Ｒ后的心脏功能，减少Ｉ／Ｒ造成的心肌肌酸激酶漏出及ＡＴＰ消耗。ＩＰＣ过程ＥＲＫｓ和ｐ３８激酶的活性分别较单纯Ｉ／Ｒ组高７３％（Ｐ＜００１）和６９％（Ｐ＞００１）；而心肌ＳＡＰＫ的活性无明显改变。预先给予酪氨酸激酶抑制剂ｇｅｎｉｓｔｅｉｎ和ＥＲＫｓ抑制剂ＰＤ０９８０５９可分别消除ＩＰＣ的上述保护作用，而ｐ３８抑制剂ＳＢ２０２１９０对ＩＰＣ无明显影响。结论ＥＲＫｓ激酶参与了ＩＰＣ的心肌保护作用，而ｐ３８和ＳＡＰＫ未参与ＩＰＣ保护机制。
Objective To investigate the cardioprotective effect of mitogenactivated protein kinases (MAPKs) of ischemic preconditioning (IPC) in rat heart HZMethods In the model of ischemia/reperfusion (I/R) of isolated perfused SD rat heart, the effect of IPC on I/R injury was observed The activities of MAPK family members, ERKs, p38 and SAPK, and their relationship with IPC phenomenon were also observed Results IPC significantly improved myocardial functions in heart subjected to I/R injury, and attenuated leakage of myocardial creatine kinase and depletion of ATP IPC activated ERK and p38 kinase Their activities were increased by 73%(P<001) and 69%(P<001) respectively However, IPC showed no effect on myocardial SAPK activity Preparation with genistein (an inhibitor of tyrosine kinase) and PD098059 (an inhibitor of ERK) abolished IPC cardioprotection, while p38 kinase inhibitor SB202190 had no effect on IPC Conclusions ERKs, but not p38 and SAPK of MAPK, mediates the IPC cardioprotective effect
出处
《中华医学杂志》
CAS
CSCD
北大核心
1999年第7期542-545,共4页
National Medical Journal of China
基金
中国博士后科学基金
