反义寡核苷酸对间质性肾炎肾小管上皮细胞骨调素表达的调节

http://www.100md.com 《中华肾脏病杂志》 2000年第5期

     作者：陈永雄 余学清 孙玉玲 陈伟英 黄凌虹 吕军

    单位：510080 广州，中山医科大学附属第一医院肾内科卫生部肾脏病临床研究重点实验室

    关键词：反义寡核苷酸；肾小管上皮细胞；骨调素；间质性肾炎

    中华肾脏病杂志000505摘 要：目的探讨骨调素(OPN)反义寡核苷酸对间质性肾炎肾小管上皮细胞OPN表达的影响。方法以一侧输尿管梗阻(UUO)所致的间质性肾炎为研究模型，肾动脉内注射全硫代修饰的OPN反义寡核苷酸，免疫组织化学双染及原位杂交技术检测OPN的表达及巨噬细胞的浸润。结果OPN及其mRNA在间质性肾炎的发展过程中表达明显升高，巨噬细胞的局部浸润均发生在过度表达OPN的肾小管周围；OPN反义寡核苷酸能显著抑制肾小管上皮细胞OPN及其mRNA的表达，减少巨噬细胞的局部浸润。结论OPN反义寡核苷酸可能通过抑制OPNmRNA转录和翻译的方式抑制肾小管上皮细胞OPN的表达。
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    Expression regulation of osteopontin by its antisense oligonucleotides in renal epithelial cells of interstitial nephritis

    CHEN Yongxiong ,YU Xueqing ,SUN Yuling,et al.

    (Department of Nephrology,First Affiliated Hospital,Sun Yat-sen University of Medical Sciences,Guangzhou 510080,China)

    Abstract：Objective To investigate the effect of antisense oligonucleotides on expression of osteopontin (OPN) in renal tubular epithelial cells of interstitial nephritis.Methods The expression of OPN and macrophage infiltration were detected in interstitial nephritis caused by unilateral ureteral obstruction (UUO) treated with OPN antisense oligonucleotides using double immunostaining and in situ hybridization.Results The expression of OPN and its mRNA was up-regulated in the development of interstitial nephritis,and macrophage infiltration occurred around tubules with up-regulated OPN expression.OPN antisense oligonucleotides inhibited the expression of OPN and its mRNA significantly in tubular cells and decreased local infiltration of macrophage.Conclusion OPN antisense oligonucleotides can inhibit OPN expression by means of preventing OPN mRNA transcription and translation.
, 百拇医药
    Keywords：Antisense oligonucleotides;Renal tubular epithelial cell;Osteopontin;Interstitial nephritis 基金项目：卫生部科研基金资助项目(98-1-090)；广东省卫生厅基金资助项目(A199814)

    参考文献：

    [1]陈永雄,李龙,尹培达,等.骨调素与肾脏疾病.中华肾脏病杂志,1999,15:57-59.

    [2]Nagasaki J,Eshimura E,Shioi A,et al.Osteopontin gene expression and protein synthesis in cultured rat mesangial cell.Biochem Biophys Res Commun,1997,223:81-85.
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    [3]Hailer H,Maasch C,Dragan D.et al.Antisense oligodesoxynucleotide strategies in renal and cardiovascular disease,Kidney Int,1998;53: 1550-1558.

    [4]余学清,陈伟英,穆威,等.CD44及其配体骨调素在人大鼠实验性新月体肾炎中的表达及作用.中华肾脏病杂志,1998, 14:79～83

    [5]Kaneto H,Morrissey J.MeCracken R,et al.Osteopontin expression in the kidney during unilateral ureteral obstruction.Miner Electrolyte Metab,1998,24:227-237.

    [6]Diamond JR,Kees-Folts D,Ricardo SD,et al.Early and persistent up-regulation of renal cortical osteopontin in experimental hydrorephrosis.Am J PathoL 1995.146:1455-1466.
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    [7]William C.Fibrosis:the dark site of repair.XV lnternational Congress of Nephrology.Burenous Aires,Argentina,1999.

    [8]Jonathan R,Diamond MS.Macrophages and progressive renal disease in experimental hydronephrosis.Am J Kidney Dis,1995,26:133-140.

    [9]Yu XQ,Nikolic-Paterson DJ,Mu W.et al.A functional role for osteopontin in experimental crescentic glomerulonephritis in the rat.Proceedings of the Association of American Physicians,1998.110:50-64.

    [10]刘红,魏东芝.反义核苷酸药物酸代磷酸酯寡核苷酸.药学进展,1997,21:1-7.

    [11]陈香美,程庆砾.重视肾脏病反义寡核苷酸治疗的研究.中华内科杂志,1998,37:147-148

    收稿日期：2000-04-18, 百拇医药

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