• 成都醫(yī)學(xué)院（成都，610081） 1 臨床醫(yī)學(xué)院，2 基礎(chǔ)醫(yī)學(xué)院形態(tài)學(xué)實(shí)驗(yàn)室;

【摘要】　 乙酰肝素酶（heparanase，HPA）是目前發(fā)現(xiàn)的哺乳動物細(xì)胞中唯一能切割細(xì)胞外基質(zhì)中硫酸肝素蛋白多糖側(cè)鏈的內(nèi)源性糖苷酶。因其可促進(jìn)腫瘤細(xì)胞的浸潤和轉(zhuǎn)移，還可以促進(jìn)腫瘤細(xì)胞生長和微血管形成，而被視為是抗腫瘤、抗炎癥的理想靶點(diǎn)。研究表明HPA可以降解腎小球基底膜硫酸乙酰肝素多糖側(cè)鏈，造成腎小球基底膜選擇性濾過蛋白質(zhì)功能下降，與糖尿病腎?。╠iabetic nephropathy，DN）蛋白尿的產(chǎn)生密切相關(guān)。HPA活性的高低對糖尿病腎病的研究有著重要的意義?，F(xiàn)將HPA與DN之間的研究進(jìn)展作一綜述。

引用本文： 安麗娜,李娟. 乙酰肝素酶與糖尿病腎病. 華西醫(yī)學(xué), 2011, 26(6): 854-856. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《華西醫(yī)學(xué)》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

1. 　葉任高, 陸再英. 內(nèi)科學(xué)[M]. 6版. 北京: 人民衛(wèi)生出版社, 2004: 794-797.
2. 　李燕杰, 李淑蓮. 乙酰肝素酶的分子特性及其在生理病理過程中的作用[J]. 河南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 27(3): 14-16.
3. 　Dong J, Kukula AK, Toyoshima M, et al. Genomic organization and chromosome localization of the newly identified human heparanase gene[J]. Gene, 2000, 253(2): 171-178.
4. 　張文娟, 任明姬. 乙酰肝素酶研究進(jìn)展[J]. 內(nèi)蒙古醫(yī)學(xué)雜志, 2010, 42(2): 202-205.
5. 　Vlodavsky I, Friedmann Y, Elkin M. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis[J]. Nat Med, 1999, 5(7): 793-802.
6. 　Mckenzie E, Tyson K, StampsA, et al. Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member[J]. Biochem Biolphy Res Commum, 2000, 276(3): 1170-1177.
7. 　Bame KJ. Heparanase:endoglycosidases that degrade heparan sulfate proteglycans[J]. Glycobiology, 2001, 11(6): 91-98.
8. 　李燕杰, 彭清忠. 乙酰肝素酶的結(jié)構(gòu)、功能及調(diào)控[J]. 生物技術(shù)通訊, 2003, 14(2): 141-144.
9. 　Raats CJ, Van Den Born J, Berden JH. Glomerular heparan sulfate alternations: mechanisms and relevance for proteinuria[J]. Kidney Int, 2000, 57(2): 385-400.
10. 　Pillarisetti S. Lipoprotein modulation of subendothelial heparan sulfate proteoglycans(perlecan)and atherogenicity[J]. Trends Cardiovasc Med, 2000, 10(2): 60-65.
11. 　倪壽翔, 李立. 乙酰肝素酶的研究進(jìn)展與眼部疾病[J]. 重慶醫(yī)科大學(xué)學(xué)報(bào), 2006, 31(1): 65-68.
12. 　閻妍, 王崢, 羅葦. 腎病鼠外周血白細(xì)胞乙酰肝素酶基因的表達(dá)及其與尿蛋白的相關(guān)性[J]. 四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2004, 35(4): 489-491.
13. 　Levidiotis V, Kanellis J, lerino FL, et al. Increased expmssion of heparanasein pummycin aminonucleoside nephrosis[J]. Kidney Int, 2001, 60(4): 1287-1296.
14. 　Katz A, Van-Dijk DJ, Aingorn H, et al. Involvement of human heparanase in the pathogenesis of diabetic nephropathy[J]. Isr Med Assoc J, 2002, 4(11): 996-1002.
15. 　Maxhimer JB, Somenek M, Rao G, et al. Heparanase-l gene expression and regulation by high glucose in renal epithelial cells: a potential role in the pathogenesis of proteinuria in diabetic patients[J]. Diabetes, 2005, 54(7): 2172-2178.
16. 　劉靜云. 淺析糖尿病腎病與尿蛋白的關(guān)系[J]. 河北中醫(yī)雜志, 2009, 31(8): 1141-1191.
17. 　唐立平, 唐政權(quán), 孫洪華. 糖尿病腎病的早期診斷及其臨床意義[J]. 中國實(shí)用醫(yī)藥雜志, 2010, 5(25): 250.
18. 　粱琳瑯, 劉國良. 糖尿病性蛋白尿用藥選擇性研究[J]. 中華內(nèi)分泌代謝雜志, 1996, 12(3): 138-140.
19. 　洪郁芝, 徐新鵬, 葉迅, 等. 糖尿病腎病蛋白尿發(fā)生機(jī)制研究進(jìn)展[J]. 中國中西醫(yī)結(jié)合腎病雜志, 2008, 9(11): 1011-1013.
20. 　Shafat I, Zcharia E, Nisman B, et al. An ELISA method for the detection and quantification of human heparanase[J]. Biochem Biophys Res Commun, 2006, 341(4): 958-963.
21. 　Zcharia E, Metzger S, Chajek-Shaul T, et al. Transgenic expression of mammalian heparanase uncovers physiological functions of heparan in tissue morphogenesis, vascularization, and feeding behavior[J]. FASEB J, 2004, 18(2): 252-263.
22. 　屈微, 張延麗. 乙酰肝素酶在妊娠期高血壓疾病大鼠腎臟的表達(dá)及低分子量肝素干預(yù)治療[J]. 中外醫(yī)療, 2010, 29(1): 24-27.
23. 　Ma P, Luo Y, Zhu X, et al. Retinal heparanase expression in streptozotocin-induced diabetic rats[J]. Can J Ophthalmol, 2010, 45(1): 46-51.
24. 　van den Hoven MJ, Rops AL, Bakker MA, et al. Increased expression of heparanase in overt diabetic nephropathy[J]. Kidney Int, 2006, 70(12): 2100-2108.
25. 　王玉華, 唐琳, 劉章鎖. 乙酰肝素酶與蛋白尿性腎臟疾病的關(guān)系[J]. 國際移植與血液凈化雜志, 2007, 5(4): 10-15.
  1. 1. 　葉任高, 陸再英. 內(nèi)科學(xué)[M]. 6版. 北京: 人民衛(wèi)生出版社, 2004: 794-797.
  2. 2. 　李燕杰, 李淑蓮. 乙酰肝素酶的分子特性及其在生理病理過程中的作用[J]. 河南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 27(3): 14-16.
  3. 3. 　Dong J, Kukula AK, Toyoshima M, et al. Genomic organization and chromosome localization of the newly identified human heparanase gene[J]. Gene, 2000, 253(2): 171-178.
  4. 4. 　張文娟, 任明姬. 乙酰肝素酶研究進(jìn)展[J]. 內(nèi)蒙古醫(yī)學(xué)雜志, 2010, 42(2): 202-205.
  5. 5. 　Vlodavsky I, Friedmann Y, Elkin M. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis[J]. Nat Med, 1999, 5(7): 793-802.
  6. 6. 　Mckenzie E, Tyson K, StampsA, et al. Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member[J]. Biochem Biolphy Res Commum, 2000, 276(3): 1170-1177.
  7. 7. 　Bame KJ. Heparanase:endoglycosidases that degrade heparan sulfate proteglycans[J]. Glycobiology, 2001, 11(6): 91-98.
  8. 8. 　李燕杰, 彭清忠. 乙酰肝素酶的結(jié)構(gòu)、功能及調(diào)控[J]. 生物技術(shù)通訊, 2003, 14(2): 141-144.
  9. 9. 　Raats CJ, Van Den Born J, Berden JH. Glomerular heparan sulfate alternations: mechanisms and relevance for proteinuria[J]. Kidney Int, 2000, 57(2): 385-400.
  10. 10. 　Pillarisetti S. Lipoprotein modulation of subendothelial heparan sulfate proteoglycans(perlecan)and atherogenicity[J]. Trends Cardiovasc Med, 2000, 10(2): 60-65.
  11. 11. 　倪壽翔, 李立. 乙酰肝素酶的研究進(jìn)展與眼部疾病[J]. 重慶醫(yī)科大學(xué)學(xué)報(bào), 2006, 31(1): 65-68.
  12. 12. 　閻妍, 王崢, 羅葦. 腎病鼠外周血白細(xì)胞乙酰肝素酶基因的表達(dá)及其與尿蛋白的相關(guān)性[J]. 四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2004, 35(4): 489-491.
  13. 13. 　Levidiotis V, Kanellis J, lerino FL, et al. Increased expmssion of heparanasein pummycin aminonucleoside nephrosis[J]. Kidney Int, 2001, 60(4): 1287-1296.
  14. 14. 　Katz A, Van-Dijk DJ, Aingorn H, et al. Involvement of human heparanase in the pathogenesis of diabetic nephropathy[J]. Isr Med Assoc J, 2002, 4(11): 996-1002.
  15. 15. 　Maxhimer JB, Somenek M, Rao G, et al. Heparanase-l gene expression and regulation by high glucose in renal epithelial cells: a potential role in the pathogenesis of proteinuria in diabetic patients[J]. Diabetes, 2005, 54(7): 2172-2178.
  16. 16. 　劉靜云. 淺析糖尿病腎病與尿蛋白的關(guān)系[J]. 河北中醫(yī)雜志, 2009, 31(8): 1141-1191.
  17. 17. 　唐立平, 唐政權(quán), 孫洪華. 糖尿病腎病的早期診斷及其臨床意義[J]. 中國實(shí)用醫(yī)藥雜志, 2010, 5(25): 250.
  18. 18. 　粱琳瑯, 劉國良. 糖尿病性蛋白尿用藥選擇性研究[J]. 中華內(nèi)分泌代謝雜志, 1996, 12(3): 138-140.
  19. 19. 　洪郁芝, 徐新鵬, 葉迅, 等. 糖尿病腎病蛋白尿發(fā)生機(jī)制研究進(jìn)展[J]. 中國中西醫(yī)結(jié)合腎病雜志, 2008, 9(11): 1011-1013.
  20. 20. 　Shafat I, Zcharia E, Nisman B, et al. An ELISA method for the detection and quantification of human heparanase[J]. Biochem Biophys Res Commun, 2006, 341(4): 958-963.
  21. 21. 　Zcharia E, Metzger S, Chajek-Shaul T, et al. Transgenic expression of mammalian heparanase uncovers physiological functions of heparan in tissue morphogenesis, vascularization, and feeding behavior[J]. FASEB J, 2004, 18(2): 252-263.
  22. 22. 　屈微, 張延麗. 乙酰肝素酶在妊娠期高血壓疾病大鼠腎臟的表達(dá)及低分子量肝素干預(yù)治療[J]. 中外醫(yī)療, 2010, 29(1): 24-27.
  23. 23. 　Ma P, Luo Y, Zhu X, et al. Retinal heparanase expression in streptozotocin-induced diabetic rats[J]. Can J Ophthalmol, 2010, 45(1): 46-51.
  24. 24. 　van den Hoven MJ, Rops AL, Bakker MA, et al. Increased expression of heparanase in overt diabetic nephropathy[J]. Kidney Int, 2006, 70(12): 2100-2108.
  25. 25. 　王玉華, 唐琳, 劉章鎖. 乙酰肝素酶與蛋白尿性腎臟疾病的關(guān)系[J]. 國際移植與血液凈化雜志, 2007, 5(4): 10-15.