参附注射液对先天性心脏病患儿心肌细胞缺血/再灌注损伤基因表达谱的影响  

Effects of Shenfu Injection on Gene Expression in Myocardial Cell with Ischemia/Reperfusion Injury in Children with Congenital Heart Disease

作　　者：顾云[1] 罗毅[2] 苏俊武[2] 吴永涛[2] 辛毅[1] 黄益民[1] 

机构地区：[1]首都医科大学附属北京安贞医院北京市心肺血管疾病研究所分子生物学研究室,北京100029 [2]首都医科大学附属北京安贞医院小儿心脏科,北京100029

出　　处：《实用儿科临床杂志》2009年第17期1355-1358,共4页Journal of Applied Clinical Pediatrics

基　　金：卫生部999中药注射液科研基金项目资助(200307)

摘　　要：目的研究参附注射液对小儿心脏直视手术期间心肌缺血/再灌注损伤的影响及其分子机制。方法选择房间隔及室间隔缺损的先天性心脏病患儿4例,分为对照组及用药组各2例。用药组患儿按体质量(2 mL/kg)给药,于阻断前10 min经体外循环一次性予参附注射液。对照组除不予参附注射液外,余条件均与用药组相同。体外循环心脏直视手术时,心肌缺血/再灌注后10 min分别采集手术结扎其右心耳部30～60 mg心肌组织,提取总RNA,利用AffymetrixTotal humamgenoe U133 plus2.0芯片进行基因差异表达分析,采用Microarray Suite 5.0软件读取,并进行数据处理。结果心肌缺血/再灌注10 min后,用药组与对照组比较,明显上调基因69条,明显下调基因134条。与心肌缺血/再灌注损伤密切相关的基因包括谷胱甘肽S转移酶、细胞色素P450、热休克蛋白、促细胞分裂激活蛋白、丝/苏氨酸激酶、钙结合蛋白、肿瘤坏死因子等基因。这些基因主要与抗氧自由基损伤、抑制细胞凋亡、心肌保护、抑制炎性反应及心肌缺血/再灌注损伤时的离子交换等机制相关。结论参附注射液对心肌起到保护作用的分子机制主要是通过调节抗氧自由基损伤相关基因、抑制心肌细胞凋亡及离子转运酶等相关基因,进而参与调控心肌缺血/再灌注损伤疾病过程中细胞信号转导过程;通过抗过氧化脂质损伤作用,减轻心肌细胞凋亡的发生,提高心肌细胞防御能力,起到保护心肌的作用。Objective To explore the possible molecular mechanisms underlying effects of Shenfu injection on ischemia/reperfusion injury during a young child open heart surgery. Methods Four children with congenital heart diseases were studied, such as atrial septal defect aud ventricular septal defect. The 4 children were divided into 2 groups, the control group （2 cases） and the injection group （2 cases）. Patients in injection group were given the one - time Shenfu injection through external circulation 10 rain before the shot off. Injection dosage was 2 mL/kg of the patient＇s body weight. The control group received the same treatments as the injection group except the Shenfu injection. During the blood eardioplegic arrest, 10 min after the reperfusion, respectively,the cardiac muscle tissue located about 30 -60 mg from the atrial appendage was collected, extracted the total RNA, the different genetic expression was analyzed by using Affymetrix Total human genome U133 plus 2.0 chips. The Microarray Suite 5.0 software was used to collect and process the data. Results Ten minutes after the ischemia/reperfusion, the injection group,compared with control group, had shown 69 significant up - regulated genes and 134 down - regulated genes. The genes that closely related to the isehemia/reperfusion injury including ：glutathione S- transferase （glutathione S- transferase 10） ,cytochrome P450 （cytochrome P450 family 1, subfamily A, polypeptide 2 ）, heat shock protein （heat shock 70 000 protein 2 ）, mitogen - activated protein, serine/threonine kinase,calcium binding protein （S100 calcium binding protein A8 ） , tumor necrosis factor, etc. These genes were primarily related to the mechanisms such as ion -exchange during the antioxidant free radical injury,anti -apoptosis,the cardiac muscle protection,the iaflammation prevention,and inhibition of the ischemia/reperfusion injury. Conclusions The molecular mechanisms of the Shenfu injection that protects the cardiac muscle is mainly through regulating the gen

关 键 词：参附注射液 缺血/再灌注损伤 心肌细胞 寡核苷酸序列分析 

分 类 号：R272[医药卫生—中医儿科学]