尽管已有的国外及我们前期研究发现钙调神经磷酸酶抑制剂除作用于T细胞等细胞外，足细胞亦为钙调神经磷酸酶抑制剂作用的靶细胞，但肾病及足细胞损伤时钙调神经磷酸酶的表达和活性变化、作用及调节机制并未澄清。本课题以足细胞中钙调神经磷酸酶为研究切入点，通过肾病大鼠及足细胞损伤模型探讨钙调神经磷酸酶的在肾病足细胞损伤中的表达和活性变化，通过特异性“敲除”和“敲低”钙调神经磷酸酶Aα和Aβ亚型证实其在肾病足细胞损伤中的重要作用；进而应用特异性抑制剂以及“敲低”技术探讨并证实我们前期实验创新性提出的肾病足细胞损伤时钙调神经磷酸酶可能受calmodulin和calpain的双重调节。探讨并不断解决该科学问题，不但补充了对肾病足细胞损伤中钙调神经磷酸酶作用的理解，理论上具有创新性，而且可能为钙调神经磷酸酶抑制剂这一“老药”在肾病治疗的药理作用机制补充新理论，为临床更合理应用钙调神经磷酸酶抑制剂提供客观实验数据。

Although the studies abroad and ours’ have found podocytes were the target of calcineurin inhibitors beside the T cells and so on, the activation, expression, role and the regulation mechanism of calcineurin in nephropathy and podocyte injury are not very clear. With the calcineurin in podocytes as a starting point, the present study will explore the activation and expression of calcineurin in kidney and podocyte through the nephrotic rats and podocyte injury model, also will explore the role of calcineurin Aα and Aβ through the podocyte-specific knockout mouse and knockdown cells model in nephropathy and podocyte injury. Moreover, our study will confirm that calcineurin may be regulated by both calmodulin and calpain in renal disease and podocyte injury. The aim of this study will not only deepen the understanding of the role of calcineurin in renal disease and podocyte injury, but also give a new theory in application of calcineurin inhibitors as the "old drug" in treating kidney diseases, and provide experimental data for reasonable application of calcineurin inhibitors in clinical practice in the future.