梓醇抑制NADPH氧化酶保护2型糖尿病早期血管内皮功能

Catalpol protect diabetic vascular endothelial function by inhibiting NADPH oxidase

该研究观察梓醇对2型糖尿病(T2DM)大鼠血管内皮功能的保护作用并探讨其抑制NADPH氧化酶表达的机制。40只高糖高脂饮食联合腹腔注射链脲佐菌素致糖尿病大鼠随机分为模型组、梓醇低、中、高剂量组(10,50,100 mg·kg-1·d-1)。另以10只健康Wistar大鼠作为正常组。正常组、模型组分别给予相当量的生理盐水。6周后全自动生化分析仪检测血糖、血脂;ELISA检测血清8-异前列腺素F2α(8-iso-PGF2α)含量;硝酸还原法检测血清一氧化氮(NO)水平;羟胺法检测血清超氧化物歧化酶(SOD)含量;观察离体胸主动脉环内皮依赖性血管舒张反应;荧光法检测主动脉组织活性氧(ROS)的水平;HE染色观察主动脉病理形态学改变;RT-PCR,western-blot分别检测主动脉组织Nox4,p22phox mRNA及蛋白表达。结果显示梓醇中、高剂量组血管内皮损伤明显减轻,主动脉ROS水平降低,血清NO水平升高,8-iso-PGF2α含量减少,SOD含量升高;主动脉组织Nox4,p22phox mRNA及蛋白表达均降低,差异均有统计学意义(P<0.05)。因此梓醇对T2DM血管内皮具有保护作用,其机制可能与其下调Nox4,p22phox表达,抑制氧化应激反应有关。

The aim of the present study was to evaluate the protective effect of catalpol on vascular endothelial function in STZinduced type 2 diabetes mellitus（T2DM） rats.40 high-fat diet with STZ-induced diabetes rats were randomly divided into model group,catalpol low-dose,middle-dose and high-dose group（10,50,100 mg·kg- 1·d- 1）,10 normal Wistar rats were used as the normal group.The normal and model groups were given an equivalent amount of saline.All reagents were administered by oral gavage for 6 weeks.After 6 weeks,blood glucose and lipids were detected by an automatic biochemical analyzer.The endothelium-dependent vasodilation response of thoracic aortar was detected.The pathological changes of the thoracic aorta were observed by HE staining.Serum nitric oxide（NO）,8-iso prostaglandin F2α（8-iso-PGF2α） and superoxide dismutase（SOD） were detected by ELISA.Reactive oxygen species（ROS） level of thoracic aorta was detected by fluorescence method.The expression of Nox4 and p22 phox mRNA and protein in aortic tissue were detected by RT-PCR and Western-blot respectively.After catalpol treatment,endothelial damage of thoracic aorta was attenuated significantly;ROS level of thoracic aorta and serum level of 8-iso-PGF2α were decreased significantly;serum NO and SOD levels were remarkably elevated;expression of Nox4,p22 phox mRNA and protein in thoracic aorta were significantly reduced（P〈0.05）.Therefore,catalpol has protective effect on endothelial of T2 DM,its mechanism may be associated with the downregulation of Nox4 and p22 phox expression,inhibiting oxidative stress reaction.response.