【作者】 谢立；

【导师】 胡冬煦； 杨一峰；

【作者基本信息】 中南大学 ， 外科学， 2012， 博士

【摘要】 目的：通过对67例肺动脉闭锁患者外科治疗进行回顾性研究,总结肺动脉闭锁,尤其是合并室间隔缺损肺动脉闭锁患者外科治疗的早期疗效,分析影响术后早期死亡的危险因素。方法：收集2005年1月-2012年2月,在我院进行手术治疗的肺动脉闭锁患者。患者术前接受心脏彩色多普勒超声等各项检查明确诊断及手术指征,接受手术治疗的67例肺动脉闭锁患者为研究对象。收集该67例肺动脉闭锁患者的住院及随访期间各种临床资料,使用医学统计学方法进行各种数据分析,总结肺动脉闭锁患者外科治疗的早期疗效,评估根治术早期手术死亡的危险因素及预后。结果：2005年1月-2012年2月中南大学湘雅二医院接受外科治疗的肺动脉闭锁患者共计67例(男35例),其中6例室间隔完整肺动脉闭锁,姑息术患者早期死亡1例,根治术患者早期死亡1例。61例合并室间隔缺损肺动脉闭锁,姑息手术患者无手术早期死亡,根治术患者手术早期死亡3例,随访期间根治术患者死亡2例。姑息手术组患者术前术后氧饱和度及McGoon比值经统计学分析有显著差异。根治手术组患者手术早期死亡单因素分析提示体外循环转流时间,McGoon比值为手术危险因素,Logistic多因素回归分析提示体外循环转流时间为手术危险因素。结论：肺动脉闭锁患者个体差异大,其外科治疗的早期疗效仍欠佳。姑息手术可显著改善合并室间隔缺损肺动脉闭锁患者的缺氧症状,并且可促进肺血管发育。体外循环时间是合并室间隔缺损肺动脉闭锁(PA-VSD)根治术手术早期死亡的危险因素。目的：研究拷贝数变异在肺动脉闭锁患者中的发生率及在先天性心脏病遗传致病机制中的作用。方法：收集2007年6月至2012年2月,湘雅二医院新生儿科,小儿心脏外科及儿科门诊或住院患者,共62例肺动脉闭锁患者样本。抽取患者及父母外周血样本,进行染色体G显带分析。提取外周血gDNA,应用SNP array芯片技术检测拷贝数变异。使用荧光定量PCR验证SNP array芯片分析结果。结果：所有62例肺动脉闭锁患者的染色体核型分析结果均为正常。使用SNP array芯片在10例肺动脉闭锁患者中共发现7个可能与肺动脉闭锁相关的拷贝数变异位点。其中4例患者CNVs位于22q11.21;2例患者CNVs位于3p26.1-26.3及10p15.1-15.3(此两例患儿为异卵双胞胎姐妹)；1例患者CNVs位于5q13.2；1例患者CNVs位于5q13.3-14.1；1例患者CNVs位于15q26.3；1例患者CNVs位于16p13.3。5q13.2缺失型CNVs,5q14.1重复型CNVs,10p15.1-15.3重复型CNVs,15q26.3重复型CNVs及16p13.3缺失型CNVs均通过Real-Time PCR加以验证,结果与芯片结果一致。结论：通过SNP array芯片分析,在62例肺动脉闭锁患者中有10例患者携带可能与肺动脉闭锁相关的拷贝数变异,其发生率为16%。除22q11.21缺失型CNVs外,其他6个CNVs均是在先天性心脏病患者中首次报道。通过生物信息学分析,5q13.2缺失型CNVs位点中包含的SMN1及SMN2基因,10p15.1-15.3重复型CNVs位点中包含的Klf6基因,15q26.3重复型CNVs位点中包含的IGF1R基因,16p13.3缺失型CNVs位点中包含的ABCA3及PKD1基因可能是先天性心脏病易感基因。更多还原

【Abstract】 Objectives:We analyzed the early outcomes of67patients with pulmonary atresia who received surgical treatment by retrospective study. In order to summarize the surgical indication,strategy and risk factors of pulmonary atresia,especially pulmonary atresia with ventricular septal defect.Methods:67patients were diagnosed as pulmonary atresia by cardiac color Doppler ultrasound,angiocardiography or64row CT cardiovascular angiography.All patients were indicated to surgical treatment,the data of hospitalization and follow-up were collected and analyzed retrospectively by statistical methods.Based on it,we assessed the risk factors and prognosis of surgical repair.Results:67cases had received surgical treatment from Jan,2005to Feb,2012in Xiangya Second Hospital,including6cases with PA-IVS and61cases with PA-VSD.There are5surgical deaths and2deaths during follow-up.4cases with PA-IVS had received palliative operation,and one died after surgery.2case with PA-IVS had undergone corrective surgery,and one died after surgery.25cases with PA-VSD had underwent palliative operation,including aorto-pulmonary shunt and right ventricle-pulmonary artery connection.The corrective surgery was performed in39cased with PA-VSD,3deaths occurred after surgery.2patients died during follow-up.The patients with PA-VSD who had received palliative operation underwent the significant relief of anoxia and the significant growth of pulmonary artery.In the patients with PA-VSD who received corrective repair,univariate analysis revealed CPB time and McGoon ratio were the risk factors of surgery,but multivariate analysis indicated CPB time was the only risk factor.Conculusions:The surgical mortality of pulmonary atrsia is unsatisfying.Palliative operation on PA-VSD showed the effects of reducing the anoxia and promoting the growth of pulmonary artery.CPB time is the risk factor of corrective operation on PA-VSD. Objectives:Studying the incidence of copy number variants in pulmonary atresia and its effects on molecular pathogenesis of congenital heart disease.Methods:Collecting the blood samples of62patients with pulmonary atresia referred to Xiangya Second Hospital from Jun,2007to Feb,2012.Using the blood samples,we performed chromosome G-banded karyotypes analysis and SNP array.Real-Time PCR was applied to confirm the results of SNP array.Results:Chromosome G-banded karyotypes analysis showed no aberration in all patients.Using SNP array,we identified7CNVs related with pulmonary atresia in10cases.22q11.21deletion was revealed in4cases.3p26.1-26.3deletion and10p15.1-15.3duplication were found in2cases(this two cases are twins).5q13.2deletion was revealed in1case.5q13.3-14.1duplication was revealed in1case.15q26.3duplication was revealed in1case.16p13.3deletion was revealed in1case. Real-Time PCR confirmed the results of SNP array.Conculusions:The incidence of CNVs in pulmonary atresia is16%.With the exception of22q11.21deletion,other6CNVs were first reported in congenital heart disease.Based on bioinfonnatics, KLF6,IGF1R,ABCA3,PKD1,SMNland SMN2genes are considered as the "candidate genes" of congenital heart disease.更多还原