目的·探讨果糖诱导肾小管上皮细胞表达单核细胞趋化蛋白-1（monocyte chemoattratant protein-1，MCP-1）的机制。方法·将HK-2细胞分为对照组，果糖孵育（1、5和10 mmol/L）组，果糖、己酮糖激酶抑制剂(KHK-IN)共孵育（果糖5 mmol/L，KHKIN分别为12、100和1 000 nmol/L）组，尿酸孵育（5、15和50 mg/dL）组，果糖、别嘌醇共孵育（果糖5 mmol/L，别嘌醇分别为0.01、0.1和0.5 mmol/L）组，尿酸、别嘌醇共孵育（尿酸50 mg/dL，别嘌醇分别为0.01、0.1和0.5 mmol/L）组，H2O2孵育（0.1和0.3 mmol/L）组，果糖、N-乙酰半胱氨酸（NAC）共孵育（果糖5 mmol/L，NAC分别为5、10和50 mmol/L）组，尿酸、NAC共孵育（尿酸50 mg/dL，NAC分别为5、10和50 mmol/L）组。采用实时荧光定量PCR和蛋白免疫印迹实验检测MCP-1 mRNA和蛋白的表达；利用活性氧（ROS）荧光探针观察果糖和尿酸对HK-2细胞ROS产生的影响。结果·果糖剂量及时间依赖性诱导HK-2细胞MCP-1 mRNA转录和蛋白表达，此过程可被KHK-IN阻断。外源性尿酸诱导HK-2细胞产生MCP-1，别嘌醇抑制果糖引起的MCP-1表达，但不能阻断外源性尿酸的作用。果糖和尿酸均诱导HK-2细胞产生ROS，别嘌醇抑制了果糖而非外源性尿酸诱导的ROS产生。H2O2诱导HK-2细胞生成MCP-1，NAC则抑制这种作用。结论·果糖在己酮糖激酶催化下，通过引起细胞内尿酸升高和产生ROS，导致人肾小管上皮细胞产生MCP-1。

Objective · To investigate the mechanism of fructose-induced monocyte chemoattratant protein-1(MCP-1) production in HK-2 cells.Methods · The HK-2 cells were divided into fructose incubated (1, 5 and 10 mmol/L) group, fructose and ketohexo-kinase inhibitor (KHK-IN) coincubation(fructose 5 mmol/L, KHK-IN was 12, 100 and 1 000 nmol/L, respectively) group, uric acid incubation (5, 15 and 50 mg/dL) group, fructoseand allopurinol co-incubation (fructose 5 mmol/L, allopurinol were 0.01, 0.1 and 0.5 mmol/L) group, uric acid and allopurinol co-incubation (uric acid 50mg/dL, allopurinol respectively 0.01, 0.1and 0.5 mmol/L) group, H2O2 incubation (0.1 and 0.3 mmol/L) group, fructose and N-acetylcysteine (NAC) coincubation(fructose 5 mmol/L, NAC respectively 5, 10 and 50 mmol/L) group, and uric acid and NAC co-incubation (uric acid 50 mg/dL, NAC was 5, 10and 50 mmol/L, respectively) group. The quantitative PCR method and Western blotting method were used to observe the of MCP-1 mRNA andprotein. The effects of fructose and uric acid on the production of ROS in HK-2 cells were observedusing a fluorescent probe. Results · Fructose dose-and time-dependently induced MCP-1 gene transcription and protein production in HK-2 cells, which could be blockedthe ketohexo-kinase blockers. Exogenous uric acid induced MCP-1 production in HK-2 cells. Allopurinol inhibited fructose, but not exogenous uric acid-induced MCP-1 . Both fructose and uric acid induced ROS generation. Incubation with H2O2 promoted MCP-1 production in HK-2 cells. NAC completely inhibited MCP-1production inducedfructose and H2O2. Conclusion · Catalyzedthe ketohexo-kinase, fructose resultes the production of MCP-1 through uric acid and reactive oxygen species.