造影剂肾病是含碘造影剂应用过程中可能发生的重要并发症，也是医源性肾功能衰竭的第三大原因，病死率高达14%。目前研究认为其发病机制主要与含碘造影剂直接或间接引起肾小管缺血、缺氧性损伤等因素有关。近年来研究发现多种microRNA与肾脏疾病相关。我们前期研究发现，经111mgI/ml低渗非离子型造影剂碘普罗胺刺激人HK-2肾小管上皮细胞制备的细胞损伤模型中，miR-371表达水平明显增加。生物信息学检测发现KL可能是miR-371的靶基因。而多种动物模型及体外实验已经证实Klotho可以有效减轻肾损伤，且预实验结果显示经造影剂刺激的HK-2肾小管上皮细胞中Klotho蛋白表达水平明显降低。因此，我们假设 “miR-371通过抑制KL表达调控造影剂肾病的发生”，拟研究miR-371对造影剂肾病发生的调控机制及其可能的下游基因。本项目的完成将为造影剂肾病的防治提供新的实验依据及治疗新靶点。

Contrast-induced nephropathy is one of the most serious complications in the iodine contrast agent application. Moreover, contrast-induced nephropathy is the third most common cause of acute kidney injury in hospitalized patients, and its case fatality rate is as high as 14% . Even though the pathogenesis is not fully clear，oxidative injuries and apoptosis are factors believed to be involved. Recently, it was reported that microRNA was involved in the regulation of nephropathy. Our pervious study found that miR-371 in HK-2 cells stimulated by 111mgI/ml iopromide (nonionic contrast medium) was significantly elevated. Bioinformatics analysis proved that KL might be the targeted gene of miR-371, while klotho was show to play an important role in the process of nephropathy. It has been proved that klotho has protective effect and therapeutic action on acute or chronic kidney disease in vivo and in vitro. Meanwhile, the expression of klotho in HK-2 cells stimulated by contrast medium was shown decreased compared to control group. Therefore, we propose our scientific hypothesis “miR-371 regulated the occurrence of kidney disease by inhibiting KL”. We will study the downstream signaling molecules of miR-371 in contrast-induced nephropathy by gain of function and loss of function using quantitative PCR, immunoblotting techniques and so on. And we intend to find the mechanism of miR-371 regulating the occurrence of kidney disease using both HK-2 cells and contrast nephropathy mouse model. The result would provide the basis to improve the mechanism of contrast-induced nephropathy and to provide experimental evidence and new targeting point for the prevention of contrast-induced nephropathy.