Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: Correlated with downregulation of LOX-1 and ICAM-1 expression on aortas
Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: Correlated with downregulation of LOX-1 and ICAM-1 expression on aortas
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DOI：
10.1016/j.ejphar.2008.08.031
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发表时间：
2008-11-12
影响因子：
5
通讯作者：
Guo Lei-ming
中科院分区：
文献类型：
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作者：
Wang Li-jun;Yu Yong-hui;Guo Lei-ming
大血管病变是糖尿病的主要并发症，其中过度氧化应激诱导的血管内皮功能障碍是早期和关键的决定因素。牛磺酸作为一种内源性抗氧化剂，在体外具有内皮保护作用。LOX-1是氧化低密度脂蛋白（oxLDL）的内皮受体，可能介导糖尿病内皮功能障碍和随后的动脉粥样硬化形成。本研究采用链脲佐菌素诱导的1型糖尿病大鼠模型，探讨牛磺酸对1型糖尿病血管内皮功能障碍的保护作用及其可能的分子机制。8只雄性Wistar大鼠作为正常对照组。16只大鼠单次注射链脲佐菌素（60 mg/kg，i. p.）糖尿病发病后随机分为糖尿病组和牛磺酸治疗组。6周后，分别测定大鼠离体胸主动脉内皮依赖性舒张功能、血清氧化低密度脂蛋白（oxLDL）、可溶性细胞间粘附分子（sICAM-1）水平及动脉瘤组织脂氧合酶（LOX-1）、细胞间粘附分子（ICAM-1）表达。链脲佐菌素诱导的糖尿病大鼠并发过度氧化应激和内皮功能障碍：血清oxLDL和sICAM-1增加，抑制内皮依赖性血管舒张反应乙酰胆碱（1 nM-0.1 μ M）。同时，LOX-1和ICAM-1的表达在糖尿病大鼠的动脉粥样硬化增强，而钝化的内皮依赖性血管舒张反应乙酰胆碱，血清oxLDL和sICAM-1水平的增加，以及LOX-1和ICAM-1的过度表达都显着减弱牛磺酸治疗。结论：牛磺酸可改善实验性1型糖尿病引起的血管内皮功能障碍，其作用机制可能与其抗氧化作用下调主动脉血管内皮LOX-1和ICAM-1的表达有关。(C)2008 Elsevier B. V.保留所有权利。
Macroangiopathy is a major complication of diabetes mellitus in which dysfunction of vascular endothelium induced by excessive oxidative stress is an early and key determinant. As an endogenous antioxidant, taurine possesses endothelial protective effect in vitro. LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL) which might mediate endothelial dysfunction and subsequent atherogenesis in diabetes. We used streptozotocin-induced rats as models of type 1 diabetes to evaluate the protective effect of taurine against vascular endothelial dysfunction in type 1 diabetes and the possibly involved molecule mechanism. Eight male Wistar rats were used as normal control group. Sixteen diabetic rats induced by one single injection of streptozocin (60 mg/kg, i.p.) were randomly divided into two groups after the diabetes onset: diabetes mellitus group and taurine-treated diabetes group. 6 weeks afterward, endothelium-dependent vasodilation of isolated thoracic aorta, serum oxLDL and soluble intercellular adhesion molecule (sICAM-1) levels, LOX-1 and intercellular adhesion molecule (ICAM-1) expression on aortas were determined respectively. Streptozocin-induced diabetic rats were complicated with excessive oxidative stress and endothelial dysfunction: increased serum oxLDL and sICAM-1, inhibited endothelium-dependent vasodilator responses to acetylcholine (1 nM-0.1 mu M). Simultaneously, LOX-1 and ICAM-I expression were enhanced in aortas of diabetic rats; whereas blunted endothelium-dependent vasodilator responses to acetylcholine, increased serum oxLDL and sICAM-1 level as well as overexpression of LOX-1 and ICAM-1 were all attenuated significantly by taurine treatment. In conclusion, taurine improves vascular endothelial dysfunction induced by experimental type 1 diabetes and this effect might be associated with downregulation of LOX-1 and ICAM-1 expression on aortic vascular endothelium via its antioxidative property. (C) 2008 Elsevier B.V. All rights reserved.