Luteolin Prevents Cardiometabolic Alterations and Vascular Dysfunction in Mice With HFD-Induced Obesity.
Luteolin Prevents Cardiometabolic Alterations and Vascular Dysfunction in Mice With HFD-Induced Obesity.
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DOI：
10.3389/fphar.2018.01094
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发表时间：
2018
影响因子：
5.6
通讯作者：
Antonioli L
中科院分区：
文献类型：
--
作者：
Gentile D;Fornai M;Pellegrini C;Colucci R;Benvenuti L;Duranti E;Masi S;Carpi S;Nieri P;Nericcio A;Garelli F;Virdis A;Pistelli L;Blandizzi C;Antonioli L
目的：木犀草素对肥胖相关的合并症有有益作用，但其对血管功能障碍的影响尚不确定。我们研究了木犀草素对饮食性肥胖小鼠内皮功能障碍的影响。方法：采用标准饲粮（SD）或高脂饲粮（HFD）小鼠每日灌胃木犀草素。8周后，评估体和附睾脂肪重量，以及血胆固醇、葡萄糖和甘油三酯。通过对乙酰胆碱的浓度-反应曲线评估耐药肠系膜血管的内皮依赖性松弛，并在nw -硝基- l -精氨酸甲基lester （L-NAME）或抗坏血酸输注后重复，分别研究一氧化氮（NO）可用性和活性氧（ROS）对内皮功能的影响。采用双氢乙啶染色法和ELISA法分别测定血管内ROS生成和TNF水平。Western blot和RT-PCR检测内皮NO合成酶（eNOS）和超氧化物歧化酶1 （SOD1）以及microRNA-214-3p的表达。结果：HFD动物的体重、附睾脂肪重量和代谢指标均有所升高。内皮依赖性松弛对L-NAME有抗性，抗坏血酸增强了内皮依赖性松弛，也恢复了L-NAME的抑制作用，提示ros依赖性降低了HFD血管中NO的可用性。此外，中腔比、血管内超氧阴离子和TNF水平升高，血管eNOS、SOD1和microRNA-214-3p表达降低。在HFD小鼠中，木犀草素抵消了身体和附睾脂肪重量的增加以及代谢改变。木犀草素恢复血管内皮NO可用性，使中腔比正常化，降低ROS和TNF水平，使eNOS、SOD1和microRNA-214-3p表达正常化。结论：木犀草素可能通过抗氧化和抗炎机制预防与肥胖相关的全身代谢改变和血管功能障碍。
Purpose: Luteolin exerts beneficial effects against obesity-associated comorbidities, although its influence on vascular dysfunction remains undetermined. We examined the effects of luteolin on endothelial dysfunction in a mouse model of diet-induced obesity. Methods: Standard diet (SD) or high-fat diet (HFD)-fed mice were treated daily with luteolin intragastrically. After 8 weeks, body and epididymal fat weight, as well as blood cholesterol, glucose, and triglycerides were evaluated. Endothelium-dependent relaxations of resistance mesenteric vessels was assessed by a concentration-response curve to acetylcholine, repeated upon Nw-nitro-L-arginine methylester (L-NAME) or ascorbic acid infusion to investigate the influence of nitric oxide (NO) availability and reactive oxygen species (ROS) on endothelial function, respectively. Intravascular ROS production and TNF levels were measured by dihydroethidium dye and ELISA, respectively. Endothelial NO synthase (eNOS) and superoxide dismutase 1 (SOD1), as well as microRNA-214-3p expression were examined by Western blot and RT-PCR assays, respectively. Results: HFD animals displayed elevated body weight, epididymal fat weight and metabolic indexes. Endothelium-dependent relaxation was resistant to L-NAME and enhanced by ascorbic acid, which restored also the inhibitory effect of L-NAME, suggesting a ROS-dependent reduction of NO availability in HFD vessels. Moreover, media-lumen ratio, intravascular superoxide anion and TNF levels were increased, while vascular eNOS, SOD1, and microRNA-214-3p expression were decreased. In HFD mice, luteolin counteracted the increase in body and epididymal fat weight, and metabolic alterations. Luteolin restored vascular endothelial NO availability, normalized the media-lumen ratio, decreased ROS and TNF levels, and normalized eNOS, SOD1 and microRNA-214-3p expression. Conclusion: Luteolin prevents systemic metabolic alterations and vascular dysfunction associated with obesity, likely through antioxidant and anti-inflammatory mechanisms.
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影响因子：
6.3
作者：
Heinonen, I.;Rinne, P.;Savontaus, E.
通讯作者：
Savontaus, E.
影响因子：
4.6
作者：
Chan, Lai-Sheung;Yue, Patrick Ying-Kit;Wong, Ricky Ngok-Shun
通讯作者：
Wong, Ricky Ngok-Shun
影响因子：
15.9
作者：
Furukawa, S.;Fujita, T.;Shimomura, I.
通讯作者：
Shimomura, I.
灯盏乙素可防止血管内皮功能障碍，并通过抗氧化预防动脉粥样硬化
影响因子：
7.9
作者：
Mo, Jiao;Yang, Renhua;Shen, Zhiqiang
通讯作者：
Shen, Zhiqiang
影响因子：
2.7
作者：
Liu, Yi;Fu, Xiaobin;Zhang, Ling
通讯作者：
Zhang, Ling