糖尿病肾病（DN）是糖尿病最主要的微血管病变之一,已成为终末期肾病的首位病因，与糖尿病患者死亡密切相关。现有研究显示基质金属蛋白酶-12（MMP-12）可以通过降解肾小球基底膜等造成非糖尿病肾病的肾损伤，临床也多集中在少数基底膜损伤的肾脏病方面，而对MMP-12在DN中的肾损伤机制及抑制MMP-12基因表达在DN中的肾保护机制仍不清楚。我们前期研究基础显示MMP-12基因表达缺失在高脂肾损伤中可以通过降低细胞外基质聚集、减少炎细胞浸润、抑制氧化应激来达到肾保护作用。本研究拟采用MMP-12基因敲除小鼠建立链尿佐菌素（STZ）诱导的DN小鼠模型，通过整体、细胞和分子水平的系列研究，来探讨MMP-12基因表达缺失在DN中是否同样通过影响细胞外基质聚集、炎细胞浸润、氧化应激及其它病理改变来发挥肾保护作用的机制。本研究有助于深入理解DN发病机制，具有重要的理论意义和潜在临床应用价值。

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes, which has become the leading cause of end-stage renal disease. DN is closely related to the death of diabetic patients. Previous studies have suggested that MMP-12 aggravate the kidney injury by degrading glomerular basement membrane in non - diabetes - renal diseases, and most of that researches just focus on a few clinical renal diseases which are related to the damage of glomerular basement membrane. However, the mechanisms of MMP-12 injury and protections of MMP-12 deletion in DN are still unclear. Our own previous studies revealed that MMP-12 deletion could play a role of renal protection in High fat diet induced renal injury by decreasing extracellular matrix accumulation, reducing inflammatory cell infiltration and inhibiting oxidative stress. In this study, we will use a mouse model induced by streptozotocin (STZ) in MMP-12 knockout mice or WT mice to investigate the mechanisms of MMP-12 deletion renal protections in DN. We will perform a series of experiments in molecular, cellular, organism and overall levels to test our hypotheses. This proposal will provide significant insights into the pathogenetic mechanisms of DN and the findings will have important theoretical significance and potential clinical theraputic value.