N-acetyl-L-cysteine inhibits activitation of p38 MAP kinase in heat stressed heart

p38丝裂原活化蛋白激酶（MAPK）在基因表达调控中起重要作用。p38 MAPK以及应激激活蛋白激酶（SAPK/JNK）被激活以响应各种细胞应激，如热应激和氧化应激。n -乙酰- l-半胱氨酸（NAC）是一种抗氧化剂，可增加细胞内谷胱甘肽（GSH）水平，减弱SAPK/JNK活性，从而减少细胞损伤。研究NAC对热应激大鼠心脏p38 MAPK活化的影响。采用戊巴比妥腹腔麻醉12只雄性Wistar大鼠。生理盐水（n=6）或1 mmol/kg NAC （n=6）在治疗前60 min ig，并测量体温。通过将动物置于正压空气培养箱中来达到所需的体温（37或41℃）。在相同体温下60分钟取出心脏。41℃时p38 MAPK活性增加到37℃时的630±53%。NAC将41℃时p38 MAPK活性的激活抑制到37℃时的127±21%。我们的结果表明，热应激和氧化应激对心脏p38 MAPK的激活有复杂的相互作用。通过抗氧化剂预处理抑制p38 MAPK活性可能是心脏热损伤器官保护的一种策略。

p38 mitogen-activated protein kinase (MAPK) plays an important role in regulating gene expression. p38 MAPK as well as stress-activated protein kinase (SAPK/JNK) is activated in response to a variety of cellular stresses, such as heat stress and oxidative stress. N-acetyl-L-cysteine ' (NAC), an antioxidant, increases the intracellular glutathione (GSH) levels and attenuates SAPK/JNK activity resulting in reduced cellular damage. We investigated the effect of NAC on the activatiomofp38 MAPK in heat stressed rat heart. 12 male Wistar rats were anesthetized with pentobarbital intraperitoneally (i.p.). Saline (n=6) or 1 mmol/kg NAC (n=6) were administered i.p. 60 min before treatment withbody temperature. Desired bodytemperature (37 or 41 C) was achieved by placing animals in a positive forced air incubator. Heart was removed 60 min follwing the samebodytemperature. p38 MAPK activity at 41 Cwas increased to 630±53 % of that at 37 C. NAC administration inhibited the activation of p38 MAPK activity at 41 C to 127± 21 % of that at 37 C. Our results indicate acomplex interactionbetweenheat stress and oxidative stress on activation of p38 MAPK in heart. Suppression of p38 MAPK activity by pretreatment with antioxidant may be one strategy for organ protection against thermal injury in heart.