文章摘要
舒〓洁,刘〓佳,蒋娟娟,王宁宁,赵秀芬,钱〓军,邢昌赢,王笑云.氟伐他汀抑制Rho激酶信号通路减少HK-2细胞纤维连接蛋白表达[J].南京医科大学学报,2010,(8):1134~1138
氟伐他汀抑制Rho激酶信号通路减少HK-2细胞纤维连接蛋白表达
Fluvastatin decreases the expression of fibronectin by inhibiting the signaling pathway of Rho-kinase in HK-2 cells
投稿时间:2010-02-28  
DOI:10.7655
中文关键词: 氟伐他汀  HK-2细胞  Rho激酶  糖尿病肾病  纤维连接蛋白
英文关键词: fluvastatin  HK-2 cells  Rho-kinase  diabetic nephropathy  fibronectin
基金项目:
作者单位
舒〓洁 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
刘〓佳 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
蒋娟娟 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
王宁宁 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
赵秀芬 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
钱〓军 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
邢昌赢 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
王笑云 南京医科大学第一附属医院肾内科,江苏 南京〓210029 
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中文摘要:
      目的:探讨Rho激酶信号通路在糖尿病肾病(diabetic nephropathy,DN)肾间质纤维化中的作用,以及氟伐他汀在防治DN肾间质纤维化中的作用机制?方法:体外培养人近端肾小管上皮细胞(HK-2细胞),Rho激酶底物肌球蛋白磷酸酶目标亚单位-1(MYPT-1)的磷酸化作为Rho激酶活化的标志?高糖刺激HK-2细胞0?6?12?24 h,不同浓度(10-7?10-6?10-5 mol/L)氟伐他汀干预12 h,Western blot检测p-MYPT-1和纤维连接蛋白(fibronectin,FN)的表达?后续实验中Western blot检测Rho激酶选择性激动剂(lysophosphatidic acid,LPA)对氟伐他汀调节HK-2细胞p-MYPT-1和FN表达的影响?结果:相对于0 h,高糖刺激HK-2细胞6?12?24 h均可以激活p-MYPT-1,其中12 h到达高峰?高糖刺激FN的表达呈时间依赖性,氟伐他汀抑制高糖诱导的HK-2细胞p-MYPT-1的活化并抑制FN的表达,并呈浓度依赖性?LPA可以拮抗氟伐他汀的作用?结论:Rho激酶信号通路可能是DN肾间质纤维化发生的始动信号之一?氟伐他汀可能通过抑制Rho激酶磷酸化进而抑制FN的表达,从而起到一定的防治DN肾间质纤维化的作用?
英文摘要:
      Objective:To explore the effect of Rho-kinase signal pathway in renal interstitial fibrosis of diabetic nephropathy(DN)and the mechanism of fluvastatin in the prevention of renal interstitial fibrosis of DN. Methods:Human renal proximal tubular epithelial cells(HK-2 cells)were cultured in vitro. Rho-kinase activity was expressed as phosphorylation of myosin-phosphatase target-1(p-MYPT-1). The level of p-MYPT-1 and fibronectin(FN) stimulated by high glucose was determined by Western blot at the time of 0 h,6 h,12 h and 24 h after treatment. Same markers were detected when HK-2 cells cultured with high glucose treated with different concentrations(10-7,10-6 and 10-5 mol/L)of fluvastatin for 12 h and treated by lysophosphatidic acid(LPA) further. Results:High glucose enhance the expression of p-MYPT-1 and FN in culured HK-2 cells at the time of 6 h,12 h and 24 h,compared with the time of 0 h. The increase of FN expression stimulated by high glucose was time-dependent and the increased level of p-MYPT-1 reached the peak at 12 h. Fluvastatin decreased the level of p-MYPT-1 and FN induced by high glucose in a dose-dependent manner. The inhibitory effect of fluvastatin on up-regulation of p-MYPT-1 and FN stimulated by high glucose can be reversed by LPA. Conclusion:Rho-kinase may be one of the initiation signals of renal interstitial fibrosis of DN. Fluvastatin can prevent the development of renal interstitial fibrosis of DN by inhibiting Rho-kinase signaling pathway.
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