心肌梗死大鼠心肌组织中AQP1、HIF-1α的表达变化及其与心肌水肿的关系
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摘要
目的观察大鼠心肌梗死模型中心肌梗死组织中水通道蛋白1(AQP1)和缺氧诱导因子-1α(HIF-1α)的表达水平,并探讨其与心肌水肿的相关性。方法将48只SD大鼠随机分为心肌梗死组和假手术组,每组24只。采用结扎左冠状动脉前降支法建立大鼠心肌梗死模型,假手术组仅开胸不结扎。于造模后12、24、48、72 h分批处死大鼠,取左心室心肌组织,采用酶联免疫法检测AQP1、HIF-1α的蛋白表达水平,采用Real-time PCR检测AQP1、HIF-1αmRNA表达,采用干湿重法检测心肌组织含水量。结果心肌梗死组大鼠心肌组织中AQP1、HIF-1αmRNA以及蛋白水平较假手术组明显升高,差异有统计学意义(P均<0.05)。心肌梗死组大鼠心肌组织AQP1、HIF-1αmRNA以及蛋白水平在术后72 h内呈时间梯度升高,各时间点差异具有统计学意义(P均<0.05)。心肌梗死组大鼠术后12、24、48、72 h心肌组织含水量逐渐升高,与假手术组比较也升高,差异有统计学意义(P均<0.05)。心肌梗死大鼠心肌组织中AQP1 mRNA以及蛋白水平与心肌含水量呈正相关(r=0.507,P=0.010;r=0.585,P=0.008),HIF-1αmRNA以及蛋白水平与心肌含水量呈正相关(r=0.408,P=0.025;r=0.486,P=0.017)。结论心肌梗死大鼠心肌组织中AQP1、HIF-1α呈高表达,且与心肌水肿严重程度明显相关。
Objective To observe the expressions of aquaporin(AQP); hypoxia-inducible factor 1α(HIF-1α) in myocardial infarction tissue, and discuss the correlation between them and myocardial edema in rat model of myocardial infarction(MI). Methods SD rats(n=48) were randomly divided into MI group and sham-operation group(each n=24). The rat model of MI was established by using ligation of left anterior descending coronary artery in MI group, and only thoracotomy without ligation in sham-operation group. The rats were killed in batches to collect left ventricular myocardial tissue after modeling for 12 h, 24 h, 48 h and 72 h. The protein expressions of AQP1 and HIF-1α were detected by using ELISA. The mRNA expressions of AQP1 and HIF-1α were detected by using real-time fluorescence quantitative polymerase chain reaction(RT-PCR). The water content in myocardial tissue was detected by using dry-wet method. Results The protein and mRNA expressions of AQP1 and HIF-1α increased significantly in MI group than those in sham-operation group(all P<0.05). The protein and mRNA expressions of AQP1 and HIF-1α increased in a time gradient in MI group after operation for 72 h, and difference at all time points had statistical significance(all P<0.05). Water content increased gradually in MI group after operation for 12 h, 24 h, 48 h and 72 h, and increased compared with sham-operation group(all P<0.05). The protein and mRNA expressions of AQP1 were positively correlated to myocardial water content(r=0.507,P=0.010;r=0.585,P=0.008) and protein and mRNA expressions of HIF-1α were positively correlated to myocardial water content(r=0.408,P=0.025;r=0.486,P=0.017). Conclusion AQP1 and HIF-1α show high expressions in myocardial tissue, and are correlated closely to severity of myocardial edema in MI rats.
Objective To observe the expressions of aquaporin(AQP); hypoxia-inducible factor 1α(HIF-1α) in myocardial infarction tissue, and discuss the correlation between them and myocardial edema in rat model of myocardial infarction(MI). Methods SD rats(n=48) were randomly divided into MI group and sham-operation group(each n=24). The rat model of MI was established by using ligation of left anterior descending coronary artery in MI group, and only thoracotomy without ligation in sham-operation group. The rats were killed in batches to collect left ventricular myocardial tissue after modeling for 12 h, 24 h, 48 h and 72 h. The protein expressions of AQP1 and HIF-1α were detected by using ELISA. The mRNA expressions of AQP1 and HIF-1α were detected by using real-time fluorescence quantitative polymerase chain reaction(RT-PCR). The water content in myocardial tissue was detected by using dry-wet method. Results The protein and mRNA expressions of AQP1 and HIF-1α increased significantly in MI group than those in sham-operation group(all P<0.05). The protein and mRNA expressions of AQP1 and HIF-1α increased in a time gradient in MI group after operation for 72 h, and difference at all time points had statistical significance(all P<0.05). Water content increased gradually in MI group after operation for 12 h, 24 h, 48 h and 72 h, and increased compared with sham-operation group(all P<0.05). The protein and mRNA expressions of AQP1 were positively correlated to myocardial water content(r=0.507,P=0.010;r=0.585,P=0.008) and protein and mRNA expressions of HIF-1α were positively correlated to myocardial water content(r=0.408,P=0.025;r=0.486,P=0.017). Conclusion AQP1 and HIF-1α show high expressions in myocardial tissue, and are correlated closely to severity of myocardial edema in MI rats.
引文
[1]王娟,刘宏斌.急性心肌梗死标记物的研究进展[J].中华老年心脑血管病杂志,2016,18(11):1213-6.
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[9]吉春玲,瞿详,任亦频,等.右美托咪定对脓毒症大鼠心肌组织水通道蛋白-1及炎症细胞因子水平的干预作用[J].中国中西医结合急救杂志,2014,21(4):266-9.
[10]Yan Y,Huang J,Ding F,et al.Aquaporin 1 plays an important role in myocardial edema caused by cardiopulmonary,bypass surgery in goat[J].Int J Mol Med,2013,31(3):637-43.
[11]李志清,肖德权,王甲汉,等.大鼠烫伤早期心肌组织水通道蛋白1表达及其与心肌水肿的关系[J].中华烧伤杂志,2013,29(3):245-8.
[12]闫玉梅,丁芳宝,梅举,等.AQP1慢病毒载体成功转染心肌细胞后加重体外循环后心肌细胞水肿[J].中华胸心血管外科杂志,2012,28(9):540-3.
[13]李继强.缺氧诱导因子1α相关信号通路与肿瘤关系的研究进展[J].医学综述,2015,21(24):4460-4.
[14]李敏,吴俊华,吴晓惠,等.伴骨髓水肿的膝骨关节炎与血管内皮因子、缺氧诱导因子1α的相关性研究[J].中华临床医师杂志(电子版),2015,9(20):19-21.
[15]靳春杰,方贵龙,权伟,等.缺氧诱导因子-1α对创伤性脑损伤大鼠炎性反应和血管生成因子表达的影响[J].中华创伤杂志,2016,32(9):835-42.
[16]李玲萍,刘艳,王丽月,等.急性心肌梗死患者血清低氧诱导因子-1α的检测及临床意义分析[J].中国药物与临床,2016,16(8):1093-5.
[2]Tahir E,Sinn MR,Radunski UK,et al.Serial native T1-and T2-mapping to quantitatively monitor resorption of myocardial edema following acute myocardial infarction[J].Journal of Cardiovascular Magnetic Resonance,2015,17(1):1-2.
[3]Akdemir G,Kaymaz F,Gursoy-?zdemir Y,et al.The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat[J].Surg Neurol Int,2016,7(1):4.
[4]戴宇翔,王审,李晨光,等.梗死心肌侧枝血管形成与缺氧诱导因子-1α及血管内皮生长因子A表达水平的关系及临床意义[J].中国临床医学,2015,22(3):305-9.
[5]王浩宇,陈玉成,曾智,等.Aquaporin-1蛋白在缺血心肌中表达变化及其与心肌水肿的关系[J].华西医学,2007,22(1):116-9.
[6]王芳,李晓娟,刘鹏飞.心肌缺血后心肌水肿的磁共振成像研究进展[J].医学综述,2015,21(13):2421-3.
[7]Fernándezjiménez R,Sánchezgonzález J,Agüero J,et al.Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern:imaging and histological tissue characterization[J].J Am Coll Cardiol,2015,65(4):315-23.
[8]魏晓,李香营,田毅,等.AQP1在心肌缺血组织中的作用[J].中国热带医学,2012,12(2):243-8.
[9]吉春玲,瞿详,任亦频,等.右美托咪定对脓毒症大鼠心肌组织水通道蛋白-1及炎症细胞因子水平的干预作用[J].中国中西医结合急救杂志,2014,21(4):266-9.
[10]Yan Y,Huang J,Ding F,et al.Aquaporin 1 plays an important role in myocardial edema caused by cardiopulmonary,bypass surgery in goat[J].Int J Mol Med,2013,31(3):637-43.
[11]李志清,肖德权,王甲汉,等.大鼠烫伤早期心肌组织水通道蛋白1表达及其与心肌水肿的关系[J].中华烧伤杂志,2013,29(3):245-8.
[12]闫玉梅,丁芳宝,梅举,等.AQP1慢病毒载体成功转染心肌细胞后加重体外循环后心肌细胞水肿[J].中华胸心血管外科杂志,2012,28(9):540-3.
[13]李继强.缺氧诱导因子1α相关信号通路与肿瘤关系的研究进展[J].医学综述,2015,21(24):4460-4.
[14]李敏,吴俊华,吴晓惠,等.伴骨髓水肿的膝骨关节炎与血管内皮因子、缺氧诱导因子1α的相关性研究[J].中华临床医师杂志(电子版),2015,9(20):19-21.
[15]靳春杰,方贵龙,权伟,等.缺氧诱导因子-1α对创伤性脑损伤大鼠炎性反应和血管生成因子表达的影响[J].中华创伤杂志,2016,32(9):835-42.
[16]李玲萍,刘艳,王丽月,等.急性心肌梗死患者血清低氧诱导因子-1α的检测及临床意义分析[J].中国药物与临床,2016,16(8):1093-5.