Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a Diabetic Mouse Model.
Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a Diabetic Mouse Model.
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二烯丙基三硫化物对糖尿病小鼠模型缺血性组织损伤和血运重建的影响
DOI：
10.1097/fjc.0000000000000579
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发表时间：
2018-06
影响因子：
3
通讯作者：
Lu ZY
中科院分区：
文献类型：
--
作者：
Yang HB;Liu HM;Yan JC;Lu ZY
背景和目的：大蒜素[二烯丙基三硫化物（DATS）]是一种从大蒜（大蒜）中提取的提取物，可以改善内皮功能，并预防心血管疾病。糖尿病患者组织缺血后的内皮功能障碍部分是由于不良的血管生成反应。本研究探讨了DATS是否可以改善糖尿病小鼠后肢缺血模型的血管生成。方法：采用链脲佐菌素腹腔注射建立雄性C57 BL/6小鼠糖尿病模型。14天后，非糖尿病和糖尿病小鼠（各n = 24）通过股动脉结扎进行单侧后肢缺血。将小鼠分成4组：非糖尿病组（或不治疗）和糖尿病组（或不治疗）。DATS治疗包括从诱导缺血当天开始每天单次腹腔注射500 g·kg-1·d-1，持续14 d。根据标准标准对缺血进行评分。使用热红外成像确定血液灌注。组织毛细血管密度和氧化应激水平分别通过免疫组织化学和免疫荧光法测定。酶比色法测定血脂。采用胰岛素酶联免疫吸附测定试剂盒检测空腹血清胰岛素。酶联免疫吸附法测定组织中一氧化氮（NO）代谢产物和蛋白质羰基。通过蛋白质印迹法测量靶蛋白浓度。结果如下：结扎后14天，与非糖尿病组相比，链脲佐菌素诱导的糖尿病小鼠的缺血骨骼肌具有较低的内皮型NO合酶、磷酸化内皮型NO合酶和血管内皮生长因子水平。此外，后肢血流灌注，毛细血管密度和NO生物活性在糖尿病组较低，而氧化应激和蛋白质羰基水平较高。DATS治疗可改善这些变化。结论：DATS治疗糖尿病小鼠可促进缺血组织的血管重建。
Background and Objective: Allitridin [diallyl trisulfide (DATS)] is an extract from garlic (Allium sativum) that putatively improves endothelial function and is protective against cardiovascular diseases. Endothelial dysfunction after tissue ischemia in diabetic patients is partially due to poor angiogenic response. This study investigated whether DATS may improve angiogenesis in a diabetic mouse model with hind limb ischemia. Methods: Streptozotocin was administered by intraperitoneal injection to establish the model of diabetes in male C57BL/6 mice. After 14 days, nondiabetic and diabetic mice (n = 24, each) underwent unilateral hind limb ischemia by femoral artery ligation. The mice were apportioned to 4 groups: nondiabetic treated (or not) with DATS and diabetic treated (or not) with DATS. DATS treatment consisted of a single daily intraperitoneal injection of 500 &mgr;g·kg−1·d−1 for 14 days, beginning on the day of induced ischemia. Ischemia was scored by standard criteria. Blood perfusion was determined using thermal infrared imaging. Tissue capillary density and oxidative stress levels were measured by immunohistochemistry and immunofluorescence, respectively. Serum lipids were measured by enzymatic colorimetric assay. Fasting serum insulin was detected using an insulin enzyme-linked immunosorbent assay kit. Nitric oxide (NO) metabolites and protein carbonyls in tissues were determined by enzyme-linked immunosorbent assay. Targeted protein concentrations were measured by western blotting. Results: At 14 days after ligation, the ischemic skeletal muscle of the streptozotocin-induced diabetic mice had lower levels of endothelial NO synthase, phosphorylated endothelial NO synthase, and vascular endothelial growth factor compared with nondiabetic group. In addition, the hind limb blood perfusion, capillary density, and NO bioactivity were lower in the diabetic group, whereas oxidative stress and protein carbonyl levels were higher. These changes were ameliorated by DATS treatment. Conclusions: DATS treatment of diabetic mice promoted revascularization in ischemic tissue.