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晚期糖基化终产物与糖尿病周围神经病变
作者:边芳,王…     文章出处:论文网     发布时间:2007-11-21
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晚期糖基化终产物与糖尿病周围神经病变

  3.3 维生素C或E 属于抗氧化剂,能够抑制二羰基化合物和AGE形成中的氧化转化反应。

  3.4 Pyrubate 属于α酮酸类化合物,推测同蛋白质中的自由酮基和自由氨基酸竞争性的形成Schiff碱防治蛋白质的糖化,也抑制初级糖基化产物经氧化反应转化为AGEs。

  3.5 重组可溶性RAGE(sRAGE) 可以抑制AGEs与细胞表面RAGE的结合和作用[16]。

  3.6 卡托普利 董砚虎等对链脲佐菌素诱导的糖尿病大鼠模型,予以卡托普利治疗12周,结果卡托普利可降低坐骨神经中糖化终产物含量,提高神经组织中cAMP的含量,部分改善坐骨神经传导速度,减轻神经的病理改变。因此卡托普利可通过降低糖基化终产物的含量,增加神经组织cAMP的生成,对糖尿病神经病变具有防治作用[17]。

  4 展望

  糖尿病已经成为当今世界上严重威胁人类健康的世界公共卫生问题。尽管糖尿病周围神经病变的机制尚未完全明了,但已有证据表明,AGEs在其发生发展中起着重要的作用。对AGEs及其与NO、氧化应激等机制的进一步研究,有利于阐明其发病机制,并将指导临床上相关的治疗策略和新药的研制和开发。

  参考文献:

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  [2] Ahmed N,Argirov OK,Minhas HS,Cordeiro CA,Thornalley PJ. Assay of advancedglycation endproducts(AGEs):surveying AGEs by chromatographic assay withderivatization by6aminoquinolgylNhydroxsuccinimidylcarbamate and applicationto Nepsiloncarboxymethyllysineand  Nepsilon(lcarboxyethyl)lysinemodifiedalbumin.Biochem J 2002 May 15;364(Pt l):114.

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  [7] Wada R,Yagihashi S.Role of advanced glycation end products and their receptorsin development of diabetic neuropathy,Ann NY Acad Sci.2005 Jun;1043:598604.

  [8] Sugimoto K,Nishizawa Y,Horiuchi S,Yagihashi S.Localization in human diabeticperipheral nerve of N(epsilon)carboxymethyllysineprotein adducts,an advancedglycation endproduct,Diabetologia.1997 Dec;40(12):13801387.

  [9] Thornalley PJ,Glycation in diabetic neuropathy:characteristics,consequences,causes,and therapeutic options,Int Rev Neurobiol.2002,50:3757.

  [10] Cellek S,Qu W,Schmidt AM,Moncada S.Synergistic action of advanced glycationend products and endogenous nitric oxide leads to neuronal apoptosis in vitro:anew insight into selective nitrergic neuropathy in diabetes.Diabetologia.2004Feb;47(2):3319.Epub 2003 Dec 16.

  [11] Singh R,Barden A,et al.Advanced glycation end products:a review.Diabetologia,2001,44:129146.

  [12] Haslbeck KM,Bierhaus A,Erwin S,et al.Receptor for advanced glycation endproduct(RAGE)mediated nuclear factorkappa B activation in vasculitic neuropathy.Muscle nerve,2004,29:853860.

  [13] 常在,陆茵.氨基胍改善糖尿病神经病变及作用机制分析[J].中国药理学通报,2005Jan,21(1):103105.

  [14] Hulme JT,Coppock EA,Felipe A,et al.Oxygen sensitivity of cloned voltagegatedK(+)channels expressed in the pulmonary vasculature.Circ Res,1999,84:489497.

  [15] Karachalias N,BabaeiJadidiR,Ahmed N,et al.Accumulation of fructosyllysinaand advanced glycation end products in the kidney,retina and peripheral nerve ofstreptozotocininduced diabetic rats.Biochem Soc Trans,2003,31:1423.

  [16] Renard C,Chappey O,Wautier MP,et al.Recombinant advanced glycation end productreceptor pharmacokinetics in normal and diabetic rats[J].  Molecularpharmacology,1997,52:5462.

  [17] 董砚虎,刘国庆,隋国良.卡托普利对糖尿病大鼠坐骨神经结构和功能的影响[J].中国内分泌代谢杂志,2001:17(04).

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