一氧化氮通过诱导热休克蛋白72的表达打开缺血预处理的第二保护窗  

Nitric oxide opens the second window of protection in is chemic preconditioning via induction of heat shock protein 72

作　　者：李伟杰[1] 贾国良[1] 郭文怡[1] 王海昌[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032

出　　处：《中国病理生理杂志》2003年第10期1386-1390,共5页Chinese Journal of Pathophysiology

摘　　要：目的 :观察在缺血预处理 (IP)过程中 ,抑制一氧化氮 (NO)的合成对热休克蛋白 72 (HSP72 )表达的影响及对缺血预处理第二保护窗的减少心肌梗死面积的影响。方法 :阻断兔冠状动脉 5min ,再灌注 10min ,重复 4次 ,完成IP。在IP前 5min ,静脉注射NO合酶抑制剂NG-硝基 -L -精氨酸甲基酯 (L -NAME) ,并持续静脉注射至整个IP过程。IP后 2 4h ,兔心脏或被快速取出测定HSP72的表达 ,或阻断冠状动脉 30min ,再灌注 12 0min ,测定心肌梗死面积。结果 :IP或假手术对照 2 4h后 ,各组之间心率和平均动脉压无明显差异。免疫印迹法显示IP组HSP72蛋白表达明显高于对照组 ,而NO合酶抑制剂L -NAME阻断了这种IP诱导的HSP72的表达。IP组心梗面积明显低于对照组 (2 9 8%± 3 7%vs 5 0 8%± 4 3% ,P <0 0 1)。经L -NAME治疗阻断了IP的缩减心梗面积的作用 (4 6 0±5 1% )。同时静脉注射L -精氨酸 ,抵消了L -NAME对IP诱导HSP72表达和心梗面积的影响 (33 5 %± 4 0 % )。静脉注射NO供体 (S -亚硝基 -N -乙酰青霉胺 ,SNAP)模仿IP ,2 4h后诱导了HSP72的表达 ,减小了心梗面积 (31 3%± 5 7% ,P <0 0 1vscontrol)。结论AIM: To examine the inhibition of nitric oxid e (NO) synthesis during ischemic preconditioning (IP) on the induction of heat s hock protein 72 (HSP72) and infarct size-limiting effect of the second window of protection. METHODS: Rabbits were subjected to 4 cycles of 5 min of coronary a r tery occlusion separated by 10 min reperfusion, or received a sham operation. Du ring this procedure, N G-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) was injected intravenously 5 min before IP followed by its continu ous infusion. Twenty-four hours later, the hearts were rapidly excised for assay ing HSP72 expression or were subjected to 30 min coronary artery occlusion follo wed by 120 min reperfusion and then measured infarct size (IS). RESULTS: Twenty-four hours later, immunoblotting revealed an inc rease in HSP72 protein levels in the IP group, and this was blocked by L-NAME. I S of the IP rabbits was reduced as compared with the control (29 8%±3 7% vs 50 8%±4 3%, P <0 01). IS in the IP rabbits was elevtated as a resul t of L-NAME treatment (46 0%±5 1%). Administration of L-arginine reversed the eff ects of L-NAME on the induction of HSP72 and IS (33 5%±4 0%). The intravenous administration of S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) increased the induction of HSP72 and reduced IS (31 3%±5 7%, P <0 01 vs c ontrol) 24 h later. CONCLUSION: These findings suggest that NO may be involved in th e induction of HSP72 and the opening of the second window of protection of IP.

关 键 词：一氧化氮 心肌梗塞 热休克蛋白质类 缺血预处理 心肌保护 

分 类 号：R542.2[医药卫生—心血管疾病]