先天性心脏病并肺动脉高压患者血清MMP-2，TIMP-2水平变化及其意义

Changes of Serum Matrix Metalloproteinase-2 and Tissue Inhibitor Metalloproteinase-2 in Patients with Congenital Heart Disease Complicating Pulmonary Hypertension

【目的】探讨先天性心脏病（CHD）并肺动脉高压（PH）患者血清基质金属蛋白酶（MMP-2）、金属蛋白酶组织抑制物（TIMP-2）水平的变化及其意义。[方法]40例左向右分流型CHD患者按肺动脉主干收缩压（SPAP）分为4组：非PH组11例（SPAP〈4．0 kPa）、轻度PH纽11例（4．0 kPa≤SPAP〈5．33 kPa）、中度PH组11例（5．33kPa≤SPAP〈9．33kPa）、重度PH组7例（SPAP≥9．33kPa）。选8例同期心内科行射频消融术患者为健康对照组。用ELISA检测其血清MMP-2和TIMP-2水平，并计算MMP-2／TIMP-2比值。【结果】①与对照组比较，CHD组MMP一2、TIMP一2和MMP-2／TIMP-2均显著增高（P〈0．01）。②非PH、轻和中、重度PH组MMP-2与对照组比较均显著增高（P〈0．01）。轻和中、重度PH组TIMP-2与对照组比较均显著增高。非PH、轻和中度PH组MMP-2／TIMP-2与对照组比较均显著增高③与非PH组比较，PH组MMP-2、TIMP-2（P〈0．01）与MMP-2／TIMP-2（P〈0．05）均增高④MMP-2与TIMP-2呈显著正相关（r=0．38，P〈0．01），TIMP-2与MMP-2／TIMP-2呈显著负相关（r=0．38，P〈0．01）。⑤CHD组下腔静脉的血清MMP-2、TIMP-2和MMP-2／TIMP-2与肺动脉相比，差异没有统计学意义（P〉0．05）。【结论】①左向右分流型CHD血清MMP-2的显著增高，且并PH患者血清TIMP-2显著升高，TIMp-2与MMP-2／TIMP-2呈显著负相关，提示MMP-2和TIMP-2参与肺血管重构全过程。②本实验将为延缓肺动脉高压形成或肺动脉高压逆转的深入研究提供一定的理论根据。

[Objective]To explore the levels and changes of serum matrix metalloproteinase-2 （MMP-2） and tissue inhibitor metalloproteinase-2 （TIMP-2） in patients with congenital heart disease（CHD） complicating pulmonary hypertension （PH） and to understand their relationship. [Methods] According to the preoperative pulmonary arterial systolic pressure （SPAP）, 40 patients with CHD were divided into4 groups： no PH group （ n =11, SPAPG4 kPa）, light PH group （ n = 11, 4. 0 kPa≤ SPAP〈5. 33 kPa）, moderate PH group （ n = 11, 5.33 kPa≤SPAP〈9.33 kPa） and heavy PH group （ n = 7, SPA≥9.33 kPa）. The concentrations of serum MMP-2 and TIMP-2 were measured with enzyme-linked imunosorbent assay（ELISA）. Then the rate of MMP-2/TIMP-2 was calculated. [ResultsI The concentrations of serum MMP 2 increased remarkably in CHD groups, compared with control group （ P 〈0.01）. The levels of TIMP-2 were also significantly advanced in all groups with PH. The rates of MMP-2/TIMP-2 in the no PH group, light PH and moderate PH group obviously increased （ P 〈0.01）. There were not obvious changes of the rate of MMP-2/TIMP-2 whether in the heavy PH group or control group （ P 〉0.05）. There were positive relationships between MMP-2 and MMP-2/TIMP-2. However, there were negative relationships between TIMP-2 and MMP-2/TIMP-2（ P 〈0.01）. No obvious changes of the levels of MMP-2 and TIMP-2 were found whether in pulmonary artery or in inferior caval vein （ P 〉0.05）. [Conclusion] The level of serum MMP-2 increases remarkably in patients with left to right shunt congenital heart disease as well as the level of TIMP-2 in congenital heart disease patients with pulmonary hypertension. TIMP-2 and MMP-2/TIMP-2 are significant negative correlation, which refers that both MMP-2 and TIMP-2 involve in the process of pulmonary vascular remodeling. This experiment will support a certain theoretical basis for further study in delaying the formation of pulmonary hypertension and reversal of pulmonary hypertension.