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Diabetologia:MMP-10或参与糖尿病微血管并发症的发生

2013-11-27 佚名 丁香园

MMP-10与糖尿病肾病和视网膜病变的关系 金属蛋白酶-10(MMP-10)在1型糖尿病中的作用尚不清楚。为了探讨金属蛋白酶-10是否在糖尿病肾病和糖尿病视网膜病变发生和发展中发挥作用,来自西班牙纳瓦拉大学Nieves Díez教授及其团队进行了一项研究,该研究发现MMP-10参与1型糖尿病微血管并发症的发生。该研究结果发表在2013年12月的Diabetologia杂志上。 


MMP-10与糖尿病肾病和视网膜病变的关系

金属蛋白酶-10(MMP-10)在1型糖尿病中的作用尚不清楚。为了探讨金属蛋白酶-10是否在糖尿病肾病和糖尿病视网膜病变发生和发展中发挥作用,来自西班牙纳瓦拉大学Nieves Díez教授及其团队进行了一项研究,该研究发现MMP-10参与1型糖尿病微血管并发症的发生。该研究结果发表在2013年12月的Diabetologia杂志上。 【原文下载】

该研究中,在269例1型糖尿病患者中测量血清MMP-10水平,并分析MMP-10与微血管并发症的关系。同时在链脲佐菌素诱导糖尿病小鼠模型中,研究敲除MMP-10基因是否影响肾损伤和视网膜损伤的程度。

该研究结果表明,MMP-10最高三分位数相关肾病和增值性视网膜病变的风险比MMP-10最低三分位数增加3到4倍,且与传统危险因素无关。相应地,MMP10-/-糖尿病小鼠的肾脏功能和形态学比MMP10+/+糖尿病小鼠保存更好。MMP10+/+糖尿病小鼠肾脏有更多的巨噬细胞浸润,提示MMP-10通过炎症反应导致微血管并发症。MMP10+/+糖尿病小鼠视网膜神经元细胞丢失多于MMP10-/-糖尿病小鼠。MMP10-/-糖尿病小鼠视网膜caspase-1水平下降,提示视网膜炎症减少。

该研究发现,MMP-10参与1型糖尿病微血管并发症的发生,而且将成为延缓糖尿病肾病和视网膜病变进展的一个潜在治疗靶点。

研究背景:

1型糖尿病是一种令人担忧的健康问题,而且其主要的微血管并发症,例如肾病和视网膜病变是发达国家终末期肾脏疾病和失明的最重要的原因。肾脏损伤之后的微量白蛋白尿在1型糖尿病中也很常见。病程15-20年后,糖尿病视网膜病变影响着80%的1型糖尿病患者。多种因素影响微血管并发症的易感性,包括血糖控制差,疾病病程,高血压,高脂血症和吸烟状况。并不是所有有风险的患者都会发生微血管并发症,而且某些患者会比其他患者花更多的时间发生微血管并发症。因此,一定有其他因素参与微血管并发症。细胞外机制调节异常参与糖尿病并发症。这部分依赖基质金属蛋白酶(MMPs),MMPs的许多亚型有境地细胞外机制和控制组织重建的作用。于是,有研究证实MMP-1和MMP-1调节异常导致1型糖尿病微血管病变的发生。目前为止,对MMP-10的研究较少。MMP-10在体外可降解III型胶原、IV型胶原、V型胶原、明胶和弹性蛋白。MMP-10可加强组织纤溶酶原激活物的纤溶活性。也有报道MPP-10参与动脉粥样硬化的血管重建。

原文出处:

Toni M, Hermida J, Goñi MJ, Fernández P, Parks WC, Toledo E, Montes R, Díez N.Matrix metalloproteinase-10 plays an active role in microvascular complications in type 1 diabetic patients.Diabetologia. 2013 Sep 27. 【原文下载】

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    2014-04-09 丁鹏鹏
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    2013-11-29 mgqwxj
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