合并室间隔缺损的大动脉转位所致肺动脉高压的可逆性程度及其分子机制

目的 探讨合并室间隔缺损(VSD)的完全性大动脉转位(TGA)所致肺动脉高压的可逆性程度及其分子机制.方法 24例平均肺动脉压力大于30 mmHg(4.0 kPa)病儿,其中大动脉转位伴室间隔缺损10例,单纯室间隔缺损14例.在体外循环开始前取其右中叶肺组织,标本经HE及弹力纤维染色,评估肺血管病变程度.ELISA检测标本中eNOS、iNOS、ET-1、ET-AR、ET-BR、MMP-2、MMP-9及TIMP的表达情况.结果 两组病儿年龄、身高、体重、VSD大小、术前肺动脉压力筹异均无统计学意义,而血红蛋白浓度、主动脉及肺动脉内氧饱和度及术后肺动脉压力下降值筹异明显,P<0.05.两组肺标本Heath-Edwards分级0～Ⅱ级,ELISA检测发现TGA组的eNOS及MMP-2表达,分别为(280.13 ±101.92)ng/mg和(31.68±15.36)ng/mg,明显低于单纯VSD组的(488.41±249.6)ng/mg和(69.28±49.12)ng/mg,P<0.05.两组iNOS、ET-1、ET-AR、ET-BR、MMP-9及TIMP表达差异无统计学意义.结论 NOS系统、ET系统及MMP/TIMP系统的失衡参与TGA合并VSD者的肺高压形成过程,相对于单纯VSD者,TGA者肺循环的高氧合状态使MMP-2和eNOS表达下调,在一定程度上影响肺动脉高压的进展及其肺血管病变的可逆性程度.

Reversibility and molecular mechanisms of pulmonary hypertension in patients with complete transposition of the great arteries combined with ventricular septal defect

Objective Explore the reversibility and potential molecular mechanisms of pulmonary hypertension in pa-tients with complete transposition of the great arteries (cTGA) combined with ventricular septal defect (VSD) in comparison with those with simple VSD. Methods Twenty-four patients with pulmonary hypertension (mean pulmonary arterial pressure was greater than 30 mmHg) were enrolled in our study, in which 10 patients suffered from cTGA with VSD, and the rest 14 pa-tients suffered from simple VSD. Lung specimens were taken from the right middle lobe of lung before cardiopulmonary bypass. The extent of pulmonary hypertension was then graded according to the Heath-Edwards classification. ELISA was used to exam-ine the expression of eNOS, iNOS, ET-1, ET-AR, ET-BR, MMP-2, MMP-9 and TIMP in all the specimens. Results No statistically significant differences in age, height, weight, the size of VSD, and the pulmonary artery pressure before operation were found between the groups. The level of hemoglobin, aortic and pulmonary arterial oxygen saturation, and the reduction value of pulmonary arterial pressure after surgery were significantly higher in the cTGA patients than that in the simple VSD pa-tients (P < 0.05). All patients had grade 0 - Ⅱ Heath-Edwards changes in their lung biopsy samples. The expression of eNOS and MMP-2 was significantly lower in the TGA group than that in the simple VSD group [eNOS: (280.13 ± 101.92) ng/mg vs. (488.41±249.6) ng/mg, P<0.05; MMP-2:(31.68±15.36)ng/mg vs. (69.28±49.12)ng/mg, P<0.05]. There were no statistically significant differences between the two groups regarding the expression of iNOS, ET-1, ET-AR, ET-BR,MMP-9 or TIMP. Conclusion The imbalance of the NOS/ET system and the MMP/TIMP system involves in the development of pulmonary hypertension in patients with TGA combined with VCD. In patients with cTGA, the high oxygenation state in pul-monary circulation may decrease the expression of MMP2 and eNOS, and may affect the progress of pulmonary hypertension to a certain extent.