腺苷A2a受体/Krüppel样因子5对缺血再灌注损伤大鼠心肌的影响  

Effects of adenosine A2a receptor/Krüppel-like factor 5 on myocardial ischemia-reperfusion injury in rats

作　　者：杜鹏辉[1] 周琦[1] 张贻凤[1] DU Penghui;ZHOU Qi;ZHANG Yifeng(Affiliated Hospital to China Geosciences University,Wuhan 430070,China)

机构地区：[1]中国地质大学医院,武汉430070

出　　处：《国际心血管病杂志》2023年第3期155-160,189,共7页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81471858)。

摘　　要：目的:探讨腺苷A2a受体/Krüppel样因子5(KLF5)对缺血再灌注损伤大鼠心肌的影响。方法:42只250~300 g雄性SD大鼠随机分为4组:假手术组(Sham组,n=6)、缺血再灌注组(I/R组,n=12)、缺血再灌注+腺苷A2a受体特异性激动剂CGS21680组(I/R+CGS组,n=12)、缺血再灌注+腺苷A2a受体拮抗剂ZM241385组(I/R+ZM组,n=12)。采用结扎左冠状动脉前降支再灌注的方法制备大鼠心肌缺血再灌注损伤模型。I/R+CGS组于再灌注前5 min静脉注射CGS21680后持续泵注60 min,CGS+ZM组于再灌注前5 min静脉注射ZM241385。于造模前,缺血5 min,再灌注10 min、45 min及120 min时分别记录各组大鼠的心率(HR)、平均动脉压(MAP)以及心率与收缩压乘积(RPP)。再灌注结束后取血液,酶联免疫吸附测定法检测血清心肌钙蛋白I(c TnI)和成纤维细胞生长因子21(FGF21)水平。再灌注结束后再次结扎左冠状动脉前降支,采用TTC染色法确定心肌梗死面积。处死大鼠,采用Western blot法检测缺血区心肌组织中的肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和KLF5的蛋白表达水平。结果:各组造模前、Sham组各时间点HR、MAP及RPP差异无统计学意义。与Sham组比较,I/R组缺血5 min时HR、MAP及RPP降低;与I/R组比较,I/R+CGS组再灌注10 min和45 min时HR、MAP及RPP降低,I/R+ZM组再灌注10 min和45 min时HR、MAP及RPP升高(P均<0.05)。与Sham组比较,I/R组心肌梗死面积增大,血清cTnI水平升高,FGF21水平降低;与I/R组比较,I/R+CGS组心肌梗死面积减小,血清cTnI水平降低,FGF21水平升高,I/R+ZM组心肌梗死面积增大,血清c TnI水平升高,FGF21水平降低(P均<0.05)。与Sham组比较,I/R组心肌组织中TNF-α、IL-1β和KLF5的蛋白表达水平均明显升高;与I/R组相比,I/R+CGS组心肌组织中TNF-α、IL-1β和KLF5的蛋白表达水平均明显降低,I/R+ZM组心肌组织中TNF-α、IL-1β和KLF5的蛋白表达水平均明显升高(P均<0.05)。结论:激活腺苷A2a受体可抑制缺血心肌细胞�Objective:To assess the effects of adenosine A2a receptor/Krüppellike factor 5 on myocardial ischemia-reperfusion(I/R)injury in rats.Methods:Forty-two male 250~300 g SD rats were randomly divided into 4 groups:sham operation group(Sham group,n=6),I/R group(n=12),I/R+adenosine A2a receptor agonist CGS21680 group(I/R+CGS group,n=12),and I/R+adenosine A2a receptor antagonist ZM241385 group(I/R+ZM group,n=12).Myocardial I/R injury model was established by ligation of left anterior descending coronary artery(LAD),which was followed by reperfusion.In I/R+CGS group,CGS21680 was injected intravenously before reperfusion and maintained for 60 min.In CGS+ZM group,ZM241385 was intravenously administered 5 min before reperfusion.For each group,heart rate(HR)and mean arterial pressure(MAP)were recorded before modeling,at 5 min post ischemia,and 10 min,45 min and 120 min after reperfusion,respectively.HR and systolic blood pressure product(RPP)was then calculated.Blood samples were collected after reperfusion,and serum levels of cardiac troponin I(cTnI)and fibroblast growth factor 21(FGF21)were determined by enzyme-linked immunosorbent assay(ELISA).After reperfusion,LAD was ligated again,and percentage ofinfarct size(IS)was detected by TTC staining.Finally,all rats were sacrificed and the expression levels of TNF-α,IL-1βand KLF5 in myocardial tissue were determined by western blot.Results:HR,MAP and RPP did not significantly differ before modeling among 4 groups and at all time pointsin Sham group,but these measurements were decreased after 5 min of ischemiain I/R group(P<0.05).Compared with I/R group,HR,MAP,and RPP were reduced after 10 min and 45 min of reperfusion in I/R+CGS group(P<0.05),but were increased in I/R+ZM group(P<0.05).Compared with Sham group,IS was significantly increased in I/R group(P<0.05).IS was reduced in I/R+CGS group(P<0.05),but increased in I/R+ZM group(P<0.05).In parallel,compared with Sham group,serum cTnI was increased and FGF21 was decreased in I/R group(all P<0.05).Serum cTnI was decreased and

关 键 词：腺苷A2A受体 Krüppel样因子5 心肌再灌注损伤 

分 类 号：R54[医药卫生—心血管疾病]