口服卡托普利预防室间隔缺损并发肺动脉高压临床疗效研究

Research on the preventive effect of oral captopril on the pulmonary arterial hypertension associated with ventricular septal defect

目的探讨常规剂量卡托普利口服预防室间隔缺损(VSD)继发肺动脉高压的效果和作用机制。方法将成都市妇女儿童中心医院2013年7月至2015年7月收治的符合纳入标准的40例VSD患儿随机均分成空白对照组和卡托普利干预组,于0、1、4、8、12周心脏超声测量肺动脉收缩压(PASP)、肺循环血流量/体循环血流量(Qp/Qs)、右室Tei指数,ELISA方法检测血浆基质金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制因子1(TIMP-1)水平,并观察药物副反应。结果 PASP、Qp/Qs、右室Tei指数、血浆MMP-9、TIMP-1水平在空白组随时间逐渐升高,而干预组随时间逐渐降低,变化趋势组间差异有统计学意义(均P<0.05)。所有指标在0周时比较差异无统计学意义(均P>0.05);1、4、8、12周4个时间点干预组PASP、右室Tei指数低于空白组(均P<0.05);4、8、12周3个时间点干预组Qp/Qs、血浆MMP-9、TIMP-1水平低于空白组(均P<0.05)。干预组患儿无一例发生药物副反应。结论对择期手术VSD患儿口服常规剂量卡托普利可改善PASP、右室Tei指数、Qp/Qs指标,可能机制之一是通过降低血浆MMP-9、TIMP-1水平,减轻肺血管重构,预防肺动脉高压,以达到最佳手术年龄。

Objective To explore the preventive effect of regular doses of captopril on the pulmonary arterial hyperten- sion associated with ventricular septal defect （VSD） and its mechanism. Methods Forty cases of children with VSD in accordance with the inclusive criteria, who were hospitalized in Chengdu Women and＇Children＇ s Central Hospital from July 2013 to July 2015 , were collected and randomly divided into blank control group （n = 20）and captopril intervention group （n = 20）. Plasma MMP-9 and TIMP-1 were examined by using ELISA, and PASP, the Qp/Qs and right ventricular Tei index were measured by cardiac color Doppler ultrasound at 0 week, 1 week, 4 weeks, 8 weeks, and 12 weeks respec- tively ; side effects in captopril intervention group were also observed. Results PASP, the Qp/Qs, right ventricular Tei index, plasma MMP-9 and TIMP-1 level in blank control group were increased over time;the same indexes in captopril intervention group were decreased, the changing trend of two groups had statistically significant difference （all P 〈 0.05 ）. The indexes were of no difference between the two groups at 0 week （all P 〉 0.05 ） ; PASP and right ventricular Tei index in captopril intervention group were lower than blank control group at 1 week, 4 weeks, 8 weeks, and 12 weeks （all P 〈 0.05） ; the Qp/Qs plasma, MMP - 9 and TIMP - 1 level in captopril intervention group were lower at 4 weeks, 8 weeks, and 12 weeks （ all P 〈 0.05 ）. No side effects were found in captopril intervention group during follow-up. Conclusion Oral regular doses of captopril in the VSD children undergoing elective surgery may reduce pulmonary vascular remodeling and prevent pulmonary hypertension in order to achieve the best age at surgery ; one of the mechanisms might be improving indexes of PASP, right ventricular Tei index and the Qp/Qs by reducing the plasma MMP 9 and TIMP - 1 level.