【作者】 夏小杰；

【导师】 曹克将； 黄元铸；

【作者基本信息】 南京医科大学 ， 内科学， 2002， 博士

【摘要】 第一部分：风心病心房颤动病人心房肌肌浆网钙操纵基因mRNA表达变化的研究 背景：房颤的发病机制十分复杂，至今尚未完全清楚，目前大多数学者认为与电重构有关。许多资料显示房颤引起的电重构与心肌细胞内Ca²⁺超负荷有关，而心肌细胞内Ca²⁺超负荷是由Ca²⁺调控基因mRNA和蛋白质的表达改变引起。对房颤电重构机理的研究，是当今房颤研究的前沿课题。 目的：研究房颤病人肌浆网钙调控基因-Ca²⁺-ATPase（SERCA）、Ryanodine受体及IP₃-I受体mRNA表达的改变，探讨房颤时心肌细胞浆Ca²⁺超负荷的原因。 方法：38例风心痛二尖瓣狭窄接受外科手术者，手术时取右心房及右心耳约各约100mg，通过RT-PCR（逆转录—聚合酶链反应）技术，以GAPDH为内参照，半定量法测量Ca²⁺-ATPase（SERCA）、Ryanodine受体及IP₃-I受体mRNA的变化。 结果：（1）风心病房颤者心房肌SERCA mRNA水平较窦性心律者下调，房颤持续时间越长者下调越明显；IP₃-I受体mRNA水平较窦性心律者上调，房颤持续时间越长上调越明显；房颤者Ryanodine受体mRNA水平较窦性心律者上调，与房颤持续时间无关。（2）钙调控基因mRNA表达与患者的年龄、性别、右房大小、中心静脉压、肺动脉楔压、二尖瓣口面积等临床参数无关；与心房不同部位无关。（3）ACEI等药物对钙调控基因mRNA表达无明显影响。 结论：房颤病人Ryanodine受体和IP₃-I受体mRNA表达上调、SERCAmRNA表达下调，说明肌浆网SERCA、Ryanodine受体及IP₃-I受体可能与房颤的发生或维持有关。更多还原

【Abstract】 Part I. Study of the expression changes of calcium_handing genes in Sarcoplamic Reticular in patients with Rheumatic Atrial FibrillationBackground: Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation (AF) is associated with intracellular calcium overload. However , the express changes of calcium-handling genes remain unclear.Objective: The study investigated the changes of the calcium_handing genes - Ca2+-ATPase( SERCA), Ryanodine and IP3-I receptors(RyR2 and IP3R1) expression in Sarcoplamic Reticular in order to explain the role of Calcium-overloading in initiation and maintenance of AF. Methods: 38 patients with mitrial stenosis undergoing open heart surgery were studied. l00mg tissue was obtained from the right appendage and the right atrium respectively. The messenger ribonucleic acid (mRNA) amount of the calcium-handing genes of Sarcoplamic Reticular was measured by reverse transcription-polymerase chain reaction (RT-PCR)and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase(GAPDH). Results: Down-regulation of SERCA in human AF; The longer the duration of AF,the more obvious is the down-regulation .Up- regulation of RyR2 and IP3R1 mRNA in human AF;The longer the duration of AF,the more obvious is the up-regulation .There were no difference between the right atriums and the right appendages.Druges have no effect in the express of Ca2+-handling genes. Conclusion: The down-regulation of SERCA, up- regulation of RyR2and IP3R1 mRNA in Sarcoplamic Reticular may have correlations with the initiation or with the maintenance of AF.更多还原