肾脏炎症是肾脏病慢性进展的关键原因，而巨噬细胞浸润与肾脏损伤程度密切相关。深入研究巨噬细胞活化机制对于阻止肾脏炎症进展具有十分重要的意义。 本课题组前期研究首次发现，巨噬细胞Mincle受体活化在肾脏炎症和损伤中发挥十分重要的作用，但巨噬细胞Mincle受体活化的机制仍不清楚，值得进一步深入研究。我们既往研究表明，蛋白尿是导致肾脏炎症的重要因素，白蛋白与TLR4活化密切相关。本研究进一步提出如下假说：白蛋白作为内源性损伤相关分子，可以通过TLR4/ NF-κB，诱导巨噬细胞Mincle受体活化，继而促进和放大肾小管间质炎症反应的发生。本课题拟通过系统的在体模式动物、细胞培养研究，阐明白蛋白/TLR4/Mincle炎症放大径路在蛋白尿引起小管间质炎症反应中的作用，为临床防治肾小管间质炎症提供新的理论依据和治疗靶点。

Renal inflammation is a common response to the kidney injury. A clear association has been established between macrophage accumulation and the severity of kidney injury. Understanding the underlying mechanism is critical for halting the kidney inflammation. Our pervious work has firstly revealed that Mincle activation in macrophage played important role in renal inflammation. However, the mechanism by which Mincle is activated remained to be clarified. We have previously demonstrated that proteinuria is important for accelerating renal inflammation and albumin is closely correlated with TLR4. Consequently, we hypothesized that in proteinuria nephropathy, albumin may activate Mincle in macrophage through TLR4/NF-κB and promote the progression of renal inflammation. In this study, We plan to test this hypothesis by performing experiments with animal model and cell culture. The aim is to demonstrate a novel amplifying loop between TLR4 and Mincle by which proteinuria promotes tubularinterstitial inflammation, and thereby to provide new therapeutic target for clinic.