中文摘要：

目的：探讨左心室在去除压力和容量负荷下心室组织基质金属蛋白酶-2和-9及金属蛋白酶组织型抑制剂-1和-2表达水平与细胞外基质沉积量的关系。方法：12周龄雄性Lewis大鼠建立Lewis-to-Lewis腹腔异位心脏移植模型，形成左心室去负荷状态，并以同龄雄性Lewis大鼠胸腔原位心脏作为对照。移植后14d采用天狼猩红-偏振光法对移植和对照组心脏的ECM沉积量进行分析。心室组织MMP-2和MMP-9活性检测采用明胶酶谱法。MMP-2、MMP-9、TIMP-1、TIMP-2的mRNA表达水平检测采用荧光定量PCR法；TIMP-1和TIMP-2蛋白含量采用Western blot测定。结果：手术后14d，与原位心脏比较，腹腔移植心脏心肌细胞横截面积减小，并伴有心肌ECM沉积量增多（胶原容积分数5．22％±1．6％VS2．21％±0．9％，P〈0．05），并且MMP-2、MMP-9明胶酶活性明显增强，MMP-2、MMP-9及其组织型抑制剂T1MP-1、TIMP-2的mRNA表达均增加（P〈0．05），但TIMP-1、TIMP-2增加幅度较MMP-2、MMP-9高，TIMP-1、TIMP-2的蛋白含量均增加（P〈0．05），TIMP-1增加幅度更为明显。结论：左心室在去除压力和容量负荷状态下心脏心室组织胶原沉积量增加，伴有MMPs／TIMPs系统失衡，尤其是TIMPs系统的明显上调。

英文摘要：

Aim： To investigate the relationship between the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 and ECM accumulation in rat left ventricle in a mechanical unloaded heart model. Methods： 12-week-old male Lewis rats were subjected to abdominal hetemtopic heart transplantation to achieve pressure and volume unloading（ mechanical unloading）. Age and sex matched in situ heart of Lewis rats were used as control. Collagen volume fraction（CVF） was analyzed by pierosiris-red staining pins polarized microscopy. MMP-2 and -9 gelatinolytic activity were measured by gelatin-zymography, mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by real-time quantitative PCR. TIMP-1 and TIMP-2 protein level were measured by immunoblotting. Results： Myocardial cross-sectional area of transplanted heart was significandy reduced, and accompanied by excessive ECM deposition（CVF 5.22% ± 1.6% vs 2.21% ± 0.9%, P 〈 0.05） compared to in situ heart. MMP-2 and MMP-9 activity were significantly increased, as well as mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 compared to in situ heart. TIMP-1 and TIMP-2 protein level in mechanically unloaded heart were significantly upregulated compared to in situ heart, especially for TIMP-1. Conclusion： Mechanical unloading of left ventricle may lead to excessive ECM deposition, accompanied by imbalance between MMPs and TIMPs system, especially the upregulation of TIMPs.