STZ诱导的糖尿病大鼠急性心肌梗死后心脏重构及相关基因的表达

目的： 研究糖尿病大鼠急性心肌梗死的心肌重构及相关基因的表达。方法：糖尿病诱导10周，未作任何治疗，结扎左前降支，透射电子显微镜检查、超声心动描记术、心脏重量与胫骨长度比、组织学变化、基因芯片、实时-PCR用于监测直至56 d的变化。结果：结扎后，糖尿病大鼠生存率显著低于非糖尿病大鼠。病理生理学变化表明DM能够加速梗死后心肌重构。根据筛选条件，选择164个与心脏重构相关的基因，例如富含亮氨酸的PPR模体（白细胞介素-6信号通路）、原骨胶原Ⅰ型和Ⅲ型、纤维连接蛋白1、RT1和TIMP-1等。无监督聚类分析发现糖尿病大鼠14 d时的基因表达与非糖尿病大鼠14 d和28 d相似，而其28 d和56 d的基因变化和非糖尿病大鼠56 d相似。结论：链佐菌素诱导的糖尿病大鼠急性心肌梗死后的心脏重构加速与心肌重构相关基因表达提前有关。

Accelerated cardiac remodeling of post-infarction was associated with changes of gene expression profile in untreated streptozotocin-induced diabetic rats

AIM: To study the time-dependent effects of diabetes mellitus (DM) on the development of cardiac remodeling in untreated streptozotocin (STZ)-induced rats with acute myocardial infarction (MI). METHODS: The left anterior descending coronary arteries were ligated 10 weeks after DM induction without any therapy. Transmission electron microscopy, echocardiography, heart weight to tibial length ratios, histological examination, microarray analysis, and real time-PCR were utilized to monitor the changes up to 56 d. RESULTS: After MI, the diabetic rats experienced lower survival rate compared to non-diabetic animals. The pathophysiologic changes indicated that DM accelerated the cardiac remodeling post-infarction. In primary examination, 164 genes related to cardiac remodeling were found to be candidates for hierarchical analysis, such as leucine-rich PPR-motif containing (interleukin-6 signaling pathway), procollagen type I and III, fibronectin-1, RT1, and TIMP-1, etc. The gene expression profile at 14 d in diabetic rats were comparably similar to both 14 d and 28 d in non-diabetic rats, while such changes at 28 d and 56 d in diabetic rats was also similar to the ones at 56 d in non-diabetic rats. CONCLUSION: The accelerated cardiac remodeling of post-infarction in STZ-induced untreated diabetic rats seems be associated with the different profile of gene expressions.