Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Curr Pharm Biotechnol. 2011 Sep;12(9):1427-39. doi: 10.2174/138920111798281135.
This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS).
Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content.
Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.
本研究旨在探讨洋葱提取物对动脉粥样硬化（AS）大鼠内源性硫化氢（H2S）和肾上腺髓质素（ADM）的影响及其对动脉粥样硬化进展的影响。
雄性 Sprague-Dawley 大鼠随机分为对照组、AS 组和 AS+洋葱组。检测主动脉超微结构和主动脉及冠状动脉粥样硬化病变。采用硫代巴比妥酸敏感电极法检测血浆和主动脉 H2S，放射免疫法检测血浆和主动脉 ADM。分析胱硫醚-γ-裂解酶（CSE）、降钙素受体样受体（CRLR）、受体活性修饰蛋白（RAMP1、RAMP2 和 RAMP3）mRNA 表达。检测血浆谷胱甘肽过氧化物酶（GSH-PX）、超氧化物歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）和一氧化氮合酶（NOS）含量，主动脉 SOD1、SOD2 和 ICAM-1 表达。AS 组大鼠主动脉和冠状动脉均有明显粥样硬化病变，但主动脉 H2S 生成减少。血浆和主动脉 ADM 含量降低，而主动脉 CRLR、RAMP2 和 RAMP3 mRNA 水平升高。血浆 GSH-PX 和 SOD 减少，MDA 升高。血浆 ICAM-1 和 NO 含量及 iNOS 活性增加。然而，洋葱提取物减轻了动脉粥样硬化病变，增加了内源性主动脉 H2S 的产生，但降低了血浆 ADM 含量、主动脉 ADM 含量和主动脉 CRLR、RAMP2 和 RAMP3 mRNA。此外，它增加了血浆 GSH-PX 水平和 SOD 活性，降低了 MDA；降低了炎症反应，但增加了血浆 eNOS 活性和 NO 含量。
洋葱提取物通过上调内源性 CSE/H2S 途径，下调 ADM/CRLR 家族，对动脉粥样硬化大鼠具有明显的抗动脉粥样硬化作用。
