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说明：
关键词： 一氧化氮(NO),糖尿病 ,血管病变
糖尿病所致的血管病变，主要与糖代谢障碍及普遍的糖基化、脂质代谢障碍等密切相关。目前大多数学者认为糖尿病血管病变与内皮功能受损密切相关，一氧化氮在其中起十分重要的作用，本文即对近年有关NO与糖尿病血管病变的一些文献作一综述。
一、NO的产生和作用机制
NO是一种可溶于水的活性气体小分子，具有亲脂性，可穿过生物膜屏障，半衰期极短，它由NO合酶(NO Synthase, NOS)催化L-精氨酸(L-Arginine, L-Arg)合成。NOS分结构型(cNOS)和诱导型(iNOS)两种，cNOS的活性依赖于Ca和钙调素(CaM)介导，主要存在于内皮细胞和神经元中，其合成的NO作为信使分子起生理作用，而iNOS的活性则不依赖Ca和CaM介导，它主要存在于巨噬细胞、中性粒细胞和肝细胞中，合成过量的NO起细胞抑制和细胞毒性作用〔1〕。
许多物质舒张血管的作用依赖于完整的血管内皮细胞释放NO，如乙酰胆碱(Acetylcholine, Ach)等。Ach引起的NO依赖的舒血管作用需通过激活可溶性鸟苷酸环化酶(sGC)，使鸟苷环一磷酸(cGMP)生成增加。而cGMP是血管平滑肌细胞的主要效应剂，可抑制平滑肌收缩，而使血管舒张〔2〕。另外，cGMP还是血小板的主要效应剂，cGMP可抑制血小板活性。对不含sGC的细胞，NO可通过非cGMP依赖途径限制细胞有丝分裂、抑制细胞增殖，从而起阻止血管粥样硬化等作用。
目录：
一、NO的产生和作用机制
二、糖尿病时NO合成减少
三、糖尿病时NO活性下降
四、小结
参考文献：
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2 Archer SL, Huang JMC, Hampl V, et al. Nitric oxide and cGMP cause vasorelaxation by activation of a charybolotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA, 1994，91:7583-7587.
3 Zimmermann PA, Knot HJ, Stevenson AS, et al. Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats. Circ Res, 1997,81:996-1004.
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6 Pieper GM, et al. Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat. Diabetologia, 1997,40:910-915.
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作者点评：
糖尿病时血管内皮依赖的血管舒张功能下降可能与下列因素有关：(1)NO合成减少；(2)NO灭活增加；(3)NO从内皮扩散到平滑肌的过程受阻；(4)一些受体功能发生改变(如NO受体下调)；(5)血管内皮释放的缩血管物质增多。
糖尿病血管病变的发生发展不是由单一因素决定的，而是多因素共同作用的结果。在糖尿病的不同阶段、不同器官占主导地位的机制可能都有不同。最近Watcher等〔17〕也提出NO在糖尿病时的变化是一个随病程改变的过程，即早期NO代偿性合成增加而晚期则合成减少。
已有不少证据表明，在糖尿病动物饮食中添加NO合成底物L-Arg可使糖尿病动物体内NO合成增加，从而延缓糖尿病血管病变的发生或改善已有的糖尿病血管病变〔5〕。最近，又有学者发现运动可以使糖尿病患者体内NO合成增加，从而延缓糖尿病内皮受损〔18〕。这些结果为临床通过增加患者体内NO水平防治糖尿病血管内皮损伤提供了依据。
