Woodman Owen L, Malakul Wachirawadee
School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia.
Life Sci. 2009 Jul 3;85(1-2):54-9. doi: 10.1016/j.lfs.2009.04.012. Epub 2009 May 3.
Diabetes increases oxidant stress and impairs endothelium-dependent relaxation. We investigated whether the antioxidant 3',4'-dihydroxyflavonol (DiOHF) reduces the release of superoxide (O(2)(-)) and preserves endothelial function in aortae from diabetic rats.
Type-1 diabetes was induced in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.) and vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence respectively.
Eight weeks after STZ treatment blood glucose was elevated (39.4+/-0.4 mM) compared to citrate treated control rats (5.5+/-0.1 mM, P<0.05) and there was an increased aortic generation of O(2)(-) (control 670+/-101, diabetic 1535+/-249 units/mg dry weight, P<0.05). In aortic rings acetylcholine (ACh)-induced relaxation was impaired (R(max) control 78+/-2, diabetic 66+/-3%, P<0.01) whereas endothelium-independent relaxation to sodium nitroprusside (SNP) was unaffected (R(max) control 100+/-1, diabetic 101+/-2%). When aortic rings were acutely exposed to DiOHF (10(-5) M) there was a significant reduction in the detection of O(2)(-) (control 124+/-15, diabetic 165+/-21 units/mg, P<0.01) and enhanced relaxation to ACh (R(max) control 84+/-3, diabetic 87+/-3%). Two separate groups of rats (control and diabetic) were treated daily with DiOHF (5 mg/kg i.p.) for 7 days. DiOHF treatment reduced superoxide generation in diabetic aortae (untreated diabetic 1471+/-358, DiOHF-treated diabetic 580+/-115 units/mg, P<0.05) and enhanced acetylcholine-induced relaxation (R(max) untreated diabetic 58+/-5, DiOHF-treated diabetic 71+/-4%, P<0.05).
DiOHF, acutely in vitro or after 1 week treatment in vivo, reduces oxidant stress and preserves endothelium-dependent relaxation in aortae from diabetic rats.
糖尿病会增加氧化应激并损害内皮依赖性舒张功能。我们研究了抗氧化剂3',4'-二羟基黄酮醇（DiOHF）是否能减少糖尿病大鼠主动脉中超氧化物（O₂⁻）的释放并维持其内皮功能。
通过链脲佐菌素（STZ）处理（55 mg/kg静脉注射）在Sprague-Dawley大鼠中诱导1型糖尿病，分别使用标准器官浴技术和光泽精增强化学发光法评估主动脉环中的血管反应性和超氧化物生成。
STZ处理8周后，与柠檬酸盐处理的对照大鼠（5.5±0.1 mM，P<0.05）相比，血糖升高（39.4±0.4 mM），并且主动脉中O₂⁻的生成增加（对照670±101，糖尿病大鼠1535±249单位/毫克干重，P<0.05）。在主动脉环中，乙酰胆碱（ACh）诱导的舒张功能受损（最大舒张率对照78±2，糖尿病大鼠66±3%，P<0.01），而对硝普钠（SNP）的非内皮依赖性舒张功能未受影响（最大舒张率对照100±1，糖尿病大鼠101±2%）。当主动脉环急性暴露于DiOHF（10⁻⁵ M）时，O₂⁻的检测量显著减少（对照124±15，糖尿病大鼠165±21单位/毫克，P<0.01），并且对ACh的舒张功能增强（最大舒张率对照84±3，糖尿病大鼠87±3%）。两组单独的大鼠（对照和糖尿病大鼠）每天腹腔注射DiOHF（5 mg/kg），持续7天。DiOHF处理减少了糖尿病大鼠主动脉中超氧化物的生成（未处理的糖尿病大鼠1471±358，DiOHF处理的糖尿病大鼠580±115单位/毫克，P<0.05），并增强了乙酰胆碱诱导的舒张功能（最大舒张率未处理的糖尿病大鼠58±5，DiOHF处理的糖尿病大鼠71±4%，P<0.05）。
DiOHF无论是在体外急性给药还是在体内给药1周后，均可减少氧化应激并维持糖尿病大鼠主动脉的内皮依赖性舒张功能。
