PI3K/Akt和JAK／STAT信号转导通路在α7nAChR激动剂后处理减轻大鼠心肌缺血再灌注损伤中的作用  

Roles of PDK/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion injury by postconditioning with αTnAChR agonist in rats

作　　者：熊军[1] 薛富善[2] 王强[2] 袁玉静[2] 廖旭[2] 程怡[2] 李瑞萍[2] 刘建华[2] 李天佐[1] 

机构地区：[1]首都医科大学附属北京同仁医院麻醉科,100730 [2]中国医学科学院北京协和医学院整形外科医院麻醉科

出　　处：《中华麻醉学杂志》2012年第7期886-889,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（8t170128）

摘　　要：目的探讨PI3K/Akt和JAK／STAT信号转导通路在订亚基烟碱型乙酰胆碱受体（α7nAChR）激动剂后处理减轻大鼠心肌缺血再灌注损伤中的作用。方法雄性SD大鼠60只，体重290～320g，采用随机数字表法，将其随机分为4组（n=15）：缺血再灌注组（I／R组）、缺血预处理组（IPC组）、缺血后处理组（IPOc组）和α7nAChR激动剂后处理组（PNU组）。4组采用结扎左冠状动脉前降支30min时进行再灌注的方法制备心肌缺血再灌注损伤模型。IPC组进行缺血预处理，缺血5min再灌注5min，共3个循环，IPOC组再灌注前进行缺血后处理，再灌注10s缺血10s，共3个循环。PNU组再灌注前即刻腹腔注射特异性α7nAChR激动剂PNU2829872．4mg／kg。再灌注60min时取5只大鼠，取心肌组织，测定AktmRNA、STAT3mRNA、磷酸化Akt（p-Akt）和磷酸化STAT3（p-STAT3）的表达水平。再灌注180min时取10只大鼠，取心肌组织，测定心肌梗死面积。结果与I／R组比较，IPC组心肌组织STAT3mRNA和p-Akt表达上调，IPOC组心肌组织p-Akt和p-STAT3表达上调，PNU组上述指标差异无统计学意义（P〉0．05），IPC组、IPOC组和PNU组心肌梗死面积缩小（P〈0．05）。结论α7nAChR激动剂后处理减轻大鼠心肌缺血再灌注损伤的机制与PI3K／Akt和JAK／STAT两条信号转导通路无关。Objective To evaluate the roles of PI3K/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion （I/R） injury by postconditioning with α subunit-containing nicotinic acetylcholine receptor （α7nAChR） agonist in rats. Methods Sixty Sprague-Dawley rats, weighing 290-320 g, were randomly divided into 4 groups （n = 15 each）： I/R group, ischemic preconditioning group （IPC group）, ischemic postconditioning group （IPOC group） and postconditioning with specific α7nAChR agonist PNU282987 group （PNU group）. Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 180 rain reperfusion in the 4 groups. The animals were subjected to 3 cycles of 5 rain myocardial ischemia and 5 rain reperfusion before 30 rain myocardial ischemia in IPC group. The animals underwent 3 cycles of 10 s myocardial ischemia at 5 s intervals before 180 min reperfusion in group IPOC. PNU282987 2.4 mg/kg was injected intraperitoneally immediately before the reperfusion. At 60 min of reperfusion, 5 rats in each group were sacrificed and the hearts were removed to determine the expression of Akt and STAT3 mRNA, phosphorylated Akt （p-Akt） and phosphorylated STAT3 （p-STAT3） in myocardial tissues. The left 10 rats in each group were sacrificed at 180 min of reperfusion and the hearts were removed to measure the infarct size. Results Compared with I/R group, the expression of STAT3 mRNA and p-Akt was significantly up-regulated in IPC group, and the expression of p-Akt and p-STAT3 was significantly up-regulated in IPOC group （ P 〈 0.05）. The infarct size was significantly reduced in IPC, IPOC and PNU groups compared with I/R group （ P 〈 0.05）. Conclusion The mechanism by which α7nAChR agonist postconditioning reduces myocardial I/R injury is not related to PI3K/Akt and JAK/ STAT signal transduction pathways in rats.

关 键 词：1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 受体 烟碱 心肌再灌注损伤 

分 类 号：R614[医药卫生—麻醉学] R-332[医药卫生—外科学]