RISK信号通路在七氟醚后处理减轻大鼠心肌缺血再灌注损伤中的作用

Role of reperfusion injury salvage kinase signaling pathway in reduction of myocardial ischemiareperfusion injury by sevoflurane postconditioning in rats

目的 评价再灌注损伤拯救激酶（RISK）信号通路在七氟醚后处理减轻大鼠心肌缺血再灌注损伤中的作用。方法 SPF级健康成年雄性SD大鼠70只，体重300～350g，采用随机数字表法分为7组（n=10）：假手术组（S组）、心肌缺血再灌注组（I／R组）、七氟醚后处理组（SP组）、磷脂酰肌醇3激酶抑制剂LY294002组（LY组）、七氟醚后处理＋LY294002组（SPLY组）、丝裂原激活蛋白激酶激酶1／2抑制利U0126组（U组）、七氟醚后处理＋U0126组（SPU组）。

Objective To evaluate the role of reperfusion injury salvage kinase signaling pathway in reduction of myocardial ischemia-reperfusion （I/R） injury by sevoflurane postconditioning in rats. Methods Seventy SPF healthy adult male Sprague-Dawley rals, weighing 300-350 g, were divided into 7 groups （n = 10 each） using a random number table： sham operation group （group S）, group l/R, sevoflurane postconditioning group （group SP）, phosphatidylinositol 3-kinase inhibitor LY294002 group （group LY）, sevoflurane posteonditioning plus LY294002 group （group SPI,Y）, mitogen-activated pro- tein kinase kinase 1/2 inhibitor U0126 group （group U） and sewJtluraue postconditioning plus U0126 group （group SPU）. Myocardial I/R was induced by occlusion of the left anterior descending branch of the coro-nary artery for 30 min followed by 120 rain of reperfusion. In group SP, 1.8% sevoflurane was inhaled for 5 min starting from the beginning of reperfusion. In LY and U groups, LY294002 0. 3 mg/kg and U0126 0.5 mg/kg were intravenously injected, respectively, at 10 min before reperfusion. In SPLY and SPU groups, LY294002 0.3 mg/kg and U0126 0.5 mg/kg were intravenously injected, respeetively, at 10 min before reperfusion, and 1.8% sevoflurane was inhaled for 5 min starting from the beginning of reperfusion. At 15 min of reperfusion, myocardial specimens were obtained from the left ventricular area at risk for determina- tion of the phosphorylation of protein kinase B （Akt） and extra-cellular signal-regulated kinase 1/2 （ERKI/2） （by Western blot） and NAD~ content in myocardial tissues （by fluoreseenee speetrophotome- try）. At the end of reperfusion, blood samples were colleeted from the jugular vein for measurement of ser- um eardiae troponin I （eTnI） eoneentrations （by photoeleetrie colorimetry） , and myocardial specimens were obtained from the left ventricular area at risk for determination of myocardial infarct size （IS）. Re- sults Compared with group S, the IS and serum cTnI concentrations were signifieantly increased, the NAD＋ content was decreased （P〈0. 05）, and no significant change was found in the phosphorylation of Akt or ERKI/2 in group I/R （P〉0.05）. Compared with group I/R, the IS and serum cTnI eoneentrations were significantly decreased, and the NAD^eontent and phosphorylation of Akt and ERK1/2 were increased in group SP （P〈0. 05） , and no significant ehange was found in the parameters mentioned above in LY, SPLY, U and SPU groups （P〉0. 05）. Compared with group SP, the IS and serum eTnI eoncentrations were significantly inereased, and the NAD＋ content was decreased in SPLY and SPU groups, the phospho- rylation of Akt was significantly decreased in group SPLY, and the phosphorylation of ERKI/2 was signifi- cantly decreased in group SPU （P〈0. 05）. Conclusion The meehanism by whieh sevoflurane posteondi- tioning reduces myoeardial I/R injury may be related to activation of reperfusion injury salvage kinase signa- ling pathway in rats.