Circulation：精氨酸酶抑制剂治疗糖尿病患者并发症

2012年11月27日 讯 /生物谷BIOON/ --近日，在一项新的发表在Circulation杂志上的研究中，卡罗林斯卡医学院和瑞典卡罗林斯卡大学医院科学家们研究揭示了精氨酸酶可能在II型糖尿病患者心血管疾病发展中起到重要组成作用。

据研究人员介绍，精氨酸酶可以防止氮氧化物对血管的保护作用，在糖尿病患者中，抑制这种酶的治疗方法能减少心绞痛的风险。

首席研究员教授Pernow说：事实上，我们可以证明精氨酸酶存在于几种类型血管壁的细胞上。糖尿病患者的并发症由血管收缩导致，后者是由斑块沉积在血管壁（动脉粥样硬化）引起。随后，血流量和氧供给的减少可导致心绞痛，心肌梗塞或中风等。

动脉粥样硬化多见于吸烟的人，但明显的是糖尿病患者拥有最高血脂水平。糖尿病和心血管疾病之间的这种相关性的原因至今未明了，科学家目前还没有具体的治疗手段来治疗这些并发症。

在此本研究中，研究人员分析了伴有心绞痛的两种类型II糖尿病患者中血管精氨酸酶的功能，并发现它可以防止血管壁保护分子一氧化氮的形成。

引入已知的物质抑制酶后，他们观察到这些患者的血管功能得到了显著改善。比较分析表明，精氨酸酶抑制剂对仅心绞痛患者没有积极效果，对健康对照组无明显影响。

目前，共有48例患者被纳入研究小组以规划一个更大的后续研究，以证实精氨酸酶抑制剂的治疗效果。

与糖尿病相关的拓展阅读：

• JAMA：研究支持对糖尿病患者进行更强力的抗血小板治疗
• Obes Surg：减重手术可能不能“治愈”糖尿病
• Cell Metab:新的血清标志物提前数年预测糖尿病风险
• Diabetologia：维生素D缺乏与1型糖尿病
• JBC：维生素D或可抑制糖尿病患者动脉的阻塞 更多信息请点击：有关糖尿病更多资讯

Arginase inhibition improves endothelial function in patients with coronary artery disease and type 2 diabetes mellitus.
BACKGROUND
Endothelial dysfunction plays an important role in the early development of atherosclerosis and vascular complications in type 2 diabetes mellitus. Increased expression and activity of arginase, metabolizing the nitric oxide substrate l-arginine, may result in reduced production of nitric oxide and thereby endothelial dysfunction. We hypothesized that inhibition of arginase activity improves endothelial function in patients with coronary artery disease (CAD) and type 2 diabetes mellitus.
METHODS AND RESULTS
Three groups of subjects were included: 16 patients with CAD, 16 patients with CAD and type 2 diabetes mellitus (CAD+Diabetes), and 16 age-matched healthy control subjects. Forearm endothelium-dependent and endothelium-independent vasodilatation were assessed with venous occlusion plethysmography before and during intra-arterial infusion of the arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA; 0.1 mg/min). Nor-NOHA was also coinfused with the nitric oxide synthase inhibitor (N(G)-monomethyl L-arginine). The expression of arginase was determined in the internal mammary artery of patients undergoing bypass surgery. Nor-NOHA markedly increased endothelium-dependent vasodilatation (up to 2-fold) in patients with CAD+Diabetes and CAD (P<0.001) but not in the control group. N(G)-monomethyl L-arginine completely inhibited the increase in endothelium-dependent vasodilatation induced by nor-NOHA. Endothelium-independent vasodilatation was slightly improved by nor-NOHA in the CAD+Diabetes group. Arginase I was expressed in vascular smooth muscle cells and endothelial cells, and arginase II was expressed in endothelial cells of patients with and without diabetes mellitus.
CONCLUSIONS
Arginase inhibition markedly improves endothelial function in patients with CAD and type 2 diabetes mellitus suggesting that increased arginase activity is a key factor in the development of endothelial dysfunction.