Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits
Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits
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DOI：
10.1177/1535370215609695
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发表时间：
2016-02-01
影响因子：
3.2
通讯作者：
Suddek, Ghada M.
中科院分区：
文献类型：
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作者：
Shehatou, George S. G.;Suddek, Ghada M.
本工作的目的是探讨萝卜硫素（SFN）对高胆固醇血症家兔动脉粥样硬化发展和内皮功能障碍的可能保护作用。将家兔分为3组，每组5只：第I组饲喂正常饲料4周，第II组饲喂1%高胆固醇饲料（HCD），第III组饲喂HCD+SFN（0.25 mg/kg/天）。检测血清甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、乳酸脱氢酶（LDH）和C反应蛋白（CRP）。测定主动脉丙二醛（MDA）、还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和总亚硝酸盐/硝酸盐（NOx）。分析血管反应性和内膜/中膜（I/M）比值。免疫组化法检测主动脉内皮细胞核因子-κ B（NF-κ B）活化。HCD诱导血清TG、TC、LDL-C、LDH和CRP以及主动脉MDA和SOD显著升高。此外，HCD引起血清HDL-C，主动脉GSH和NOx显着降低。SFN给药显著降低了HCD诱导的血清TC、LDL-C、CRP和LDH升高。升高HDL-C和GSH水平，恢复主动脉SOD和NOx水平。此外，SFN显著改善兔主动脉对乙酰胆碱的内皮依赖性舒张。此外，SFN显著降低了I/M比的升高。主动脉组织病理学检查证实了这一效应。SFN治疗后主动脉组织中NF-κ B B的表达显著降低。总之，这项研究表明，SFN有能力改善HCD诱导的动脉粥样硬化病变进展和血管功能障碍，可能通过其降脂和抗氧化作用和抑制NF-κ B介导的炎症。
The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD+SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-kappa B) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-kappa B in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-kappa B-mediated inflammation.