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Midkine反义寡聚脱氧核苷酸对糖尿病肾病大鼠肾脏CTGF表达水平的影响 被引量:1

Effect of midkine antisense oligonucleotides on the expression of CTGF in kidney of rats with diabetic nephropathy
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摘要 目的:研究中期因子(MK)反义寡聚脱氧核苷酸(AS-ODNs)对早期糖尿病肾病(DN)大鼠肾脏结缔组织生长因子(CTGF)表达水平的影响,揭示MK AS-ODNs在早期DN中的治疗前景。方法:将SD大鼠完全随机分为正常组、DN组和MK AS-ODNs组各20只,DN组和MK AS-ODNs组行单肾切+高糖高脂饲料+链脲佐菌素(STZ)建立糖尿病模型。成模第6周,MK AS-ODNs组尾静脉注射MK AS-ODNs,正常组和DN组予等量生理盐水,干预4 d后处死并留取肾脏组织,利用实时荧光定量PCR技术检测肾脏组织MK及CTGF的表达情况。结果:DN组大鼠肾脏MK和CTGF的表达水平较正常组明显增多且差异有统计学意义(P<0.05);MK AS-ODNs组大鼠肾脏MK和CTGF的表达水平较DN组明显减少且差异有统计学意义(P<0.05);MK与CTGF在大鼠肾脏组织的表达呈正相关(r=0.498,P<0.05)。结论:早期DN大鼠肾脏MK和CTGF的表达增多,MK AS-ODNs通过抑制MK的合成降低CTGF的表达水平,延缓DN进展。 Objective: To investigate the effect of midkine(MK) antisense oligodeoxynucleortides(AS-ODNs) on the expression of connective tissue growth facter(CTGF) in kidney of rats with diabetic nephropathy(DN).Methods: Sprague-Dawlry rats were randomly divided into normal control group(n=20),DN group(n=20) and MK AS-ODNs group(n=20).DN group and MK AS-ODNs group were treated with high-glucose and high-fat diet and intravenous injection STZ after unilateral nephritic excision.At the end of 6th week after diabetes mellitus model established,rats in MK AS-ODNs group were administrated with MK AS-ODNs,while normal control group and DN group were administrated with saline.After 4 days of intervention,the kidneys were rapidly dissected and stored for immunohistochemical and fluorescence quantitative PCR analyses.Results: The expression of MK and CTGF in DN group were increased significantly compared with that in normal group(P0.05).The expression of MK and CTGF in kidney of MK AS-ODNs group were decreased compared with that in DN group(P0.05).There were positive correlations between the expression of MK and CTGF in kidney of rat(r=0.498,P0.05).Conclusion: The expression of MK and CTGF in rats with DN are increasing,MK AS-ODNs can inhibit the expression of MK and CTGF and then slow down the progress of DN.
出处 《天津医科大学学报》 2012年第1期21-23,共3页 Journal of Tianjin Medical University
基金 天津市卫生局科技基金资助项目(09kz113)
关键词 糖尿病肾病 中期因子 结缔组织生长因子 反义寡聚脱氧核苷酸技术 大鼠 diabetic nephropathy midkine connective tissue growth facter antisense oligodeoxynucleortide technique rat
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参考文献11

  • 1Kosugi T,Yuzawa Y,Sato W. Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy[J].Laboratory Investigation,2007,(09):903.doi:10.1038/labinvest.3700599.
  • 2Sato W,Takei Y,Yuzawa Y. Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion[J].Kidney International,2005,(04):1330.doi:10.1111/j.1523-1755.2005.00210.x.
  • 3Burns W C,Twigg S M,Forbes J M. Connective tissue growth factor plays an important role in advanced glycation end product induced tubular epithelial-to-mesenchymal transition:Implications for diabetic renal disease[J].Journal of the American Society of Nephrology,2006,(09):2484.
  • 4陈超,蒋建伟,周序珑,严玉霞,吴颜晖,陈涛,张小鹰.CTGF反义寡核苷酸对大鼠肾间质纤维化的影响[J].广东医学,2008,29(11):1800-1802. 被引量:2
  • 5Muramatsu T. Midkine,a heparin-binding cytokine with multiple roles in development,repair and disease[J].Proceedings of the Japan Academy,2010,(04):410.
  • 6Muramatsu T. Midkine,a promising molecule for drug development to treat diseases of the central nervous system[J].Current Pharmaceutical Design,2011,(05):410.doi:10.2174/138161211795164167.
  • 7Kosugi T,Yuzawa Y,Sato W. Growth factor midkine is involved in the pathogenesis of diabetic nephropathy[J].American Journal of Pathology,2006,(01):9.doi:10.2353/ajpath.2006.050488.
  • 8Takei Y,Kadomatsu K,Matsuo S. Antisense oligodeoxynucleotide targeted to midkine,a heparin-binding growth factor,suppresses tumorigenicity of mouse rectal carcinoma cells[J].Cancer Research,2001,(23):8486.
  • 9Rappaport J,Hanss B,Kopp J B. Transport of phosphorothioate ligodeoxynucleotides in kidney:Implications ofmolecular therapy[J].Kidney International,1995,(05):1462.doi:10.1038/ki.1995.205.
  • 10Dai L C,Wang X,Yao X. Antiserse oligonucleotide targeting midkine suppresses in vivo angiogenesis[J].World Journal of Gastroenterology,2007,(08):1208.

二级参考文献8

  • 1王芳,蒋建伟,陈涛,曹明溶.聚乙烯亚胺介导生存素反义核酸体外投递肝癌SMMC-7721细胞的条件优化[J].暨南大学学报(自然科学与医学版),2006,27(4):551-556. 被引量:9
  • 2EDDY A A. Molecular insights into renal interstitial fibrosis [ J']. Am Soc Nephrol, 1996, 7( 12): 2 495-2 508.
  • 3QI w, CHEN X, PORONNIK P, et al. Transforming growth factor -β/connective tissue growth factor axis in the kidney[ J]. Int J Biochem Cell Biol, 2008, 40 ( 1 ) : 9 - 13.
  • 4QI W, CHEN X, PORONNIK P, et al. The renal cortical fibroblast in renal tubulointerstitial fibrosis[J]. Int J Biochem Cell Biol, 2006, 38 (1): 1-5.
  • 5BOHLE A, MULLER G A, WEHRMANN M, et al. Pathogenesis of chronic renal failure in the primary glmerulopathies,renal vasculopathies, and chronic interstitial nephritides [ J ]. Kidney Int, 1996, 49( Suppl. 54) : S2 - S9.
  • 6STRUTZ F. Novel aspects of renal fibrogenesis [ J ]. Nephrol Dial Transplant, 1995, 10(9): 1 526- 1 532.
  • 7FAN J M, NG Y Y, HILL P A, et al. Transforming growth factor - beta regulates tubular epithelial - myofibroblast transdifferentiation in vitro[J]. Kidney Int, 1999, 56(4) : 1 455 -1 467.
  • 8LIU Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention[ J ]. Am Soc Nephrol, 2004, 15 ( 1 ) : 1 - 12.

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