丝裂素活化蛋白激酶途径在缺氧复合烧伤血清致心肌细胞损伤中的作用  

Role of mitogen-activated protein kinases signal pathway in cardiomyocyte injury induced by serum after hypoxia and burn injury

作　　者：张家平[1] 黄跃生[1] 杨宗城[1] 

机构地区：[1]第三军医大学西南医院全军烧伤研究所,创伤,烧伤与复合伤国家重点实验室,重庆400038

出　　处：《中国危重病急救医学》2005年第3期150-153,共4页Chinese Critical Care Medicine

基　　金：国家重点基础研究发展规划项目 (G19990 5 42 0 2 ) ;国家杰出青年科学基金项目 (3 0 12 5 0 40 ) ;国家自然科学青年科学基金项目 (3 0 3 0 0 3 66) ;全军医药卫生科研基金课题 (0 1L 0 66)

摘　　要：目的　观察缺氧复合烧伤血清对心肌细胞丝裂素活化蛋白激酶 (MAPKs)活化的影响 ,探讨MAPKs信号途径在缺氧复合烧伤血清致心肌细胞损伤中的作用。方法　乳鼠心肌细胞原代培养 ,缺氧复合烧伤血清作用心肌细胞后不同时间点用免疫印迹化学发光法检测 p38激酶、细胞外信号调节激酶 (ERK)和c Jun氨基末端蛋白激酶 (JNK)磷酸化程度 ;分别用 p38激酶特异抑制剂 SB2 0 35 80和 ERK特异抑制剂PD980 5 9抑制 p38激酶和 ERK途径 ,观察其对缺氧复合烧伤血清培养条件下心肌细胞活性和培养上清中乳酸脱氢酶 (L DH)含量的影响。结果　心肌细胞 p38激酶和 ERK在缺氧复合烧伤血清作用后迅速、持续活化 ,而 JNK活化不明显。用 SB2 0 35 80抑制 p38激酶可显著减少细胞 L DH漏出 (各时间点 P<0 .0 5或 P<0 .0 1)和改善细胞活性 (双因素作用 12 h后 ,两者间比较 ,P均 <0 .0 1) ;相反 ,抑制 ERK途径在一定程度上增加了细胞 L DH漏出和降低细胞活性 (双因素作用 6 h和 12 h,两者间比较 ,P均 <0 .0 1)。结论　心肌细胞 MAPKs的 3条信号转导途径中 ,p38激酶途径和 ERK途径介导了缺氧复合烧伤血清刺激信号的胞内转导。其中 p38激酶途径激活介导了心肌细胞的损伤效应 ,而 ERK途径激活则有一定的细胞保护作用。Objective To observe the activation and explore the role of three major mitogenactivated protein kinases (MAPKs), including extracelluar signalregulated kinase (ERK), p38 kinase and cJun NH 2terminal protein kinase (JNK), in cardiomyocytes injury induced by serum after hypoxia and burn injury. Methods Phosphorylation of the three major MAPKs in primary cultured neonatal rat cardiomyocytes were determined by Western blotting. Contents of released lactate dehydrogenases (LDH) and deathrate of myocytes treated with serum after hypoxia and burn injury, SB203580+hypoxia and burn serum,PD98059+hypoxia and burn serum were observed respectively. Results Exposing rat neonatal cardiomyocytes to hypoxia and burn serum resulted in a rapid and prolonged activation of p38 kinase and ERK. Phosphorylation degree of p38 kinase, ERK1/2 was increased. Myocytes treated with SB203580 (10 μmol/L), a selective inhibitor of p38 kinase, resulted in a significant decline in LDH leakage leaking and cell death. However, with pretreatment of cell with PD98059(25 μmol/L), an inhibitor of ERK, LDH leakge and cell death were increased. Conclusion Serum obtained after hypoxia and burn injury activate p38 kinase and ERK, but not JNK, in cardiomyocytes. p38 kinase pathway might play a role in mediating cardiomyocytes injury, whereas ERK plays a protective role.

关 键 词：丝裂素活化蛋白激酶 缺氧损伤 烧伤 血清 心肌细胞损伤 激活途径 

分 类 号：R644[医药卫生—外科学] R542.2[医药卫生—临床医学]