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左旋肉碱及其丙酸盐:通过超氧化物歧化酶依赖性机制改善自发性高血压大鼠的内皮功能

l-carnitine and its propionate: improvement of endothelial function in SHR through superoxide dismutase-dependent mechanisms.

作者信息

de Sotomayor Maria Alvarez, Mingorance Carmen, Rodriguez-Rodriguez Rosalía, Marhuenda Elisa, Herrera Maria Dolores

机构信息

Departamento de Farmacologia, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain.

出版信息

Free Radic Res. 2007 Aug;41(8):884-91. doi: 10.1080/10715760701416467.

DOI:10.1080/10715760701416467
PMID:17654045
Abstract

To clarify the mechanism underlying the antioxidant properties of l-carnitine (LC) and propionyl-l-carnitine (PLC) on spontaneously hypertensive (SHR) and normotensive WKY, animals were treated with either PLC or LC (200 mg kg(- 1)). Aorta was dissected and contraction to (R)-( - )-phenylephrine (Phe) and relaxation to carbachol (CCh) were assessed in the presence or not of the NO synthase (NOS) inhibitor, l-NAME. [image omitted] production was evaluated by lucigenin-enhanced chemiluminescence and its participation on relaxation was observed after incubation with superoxide dismutase (SOD) plus catalase. Protein expressions of eNOS, Cu/Zn-SOD and Mn-SOD were studied by western blot. Both LC and PLC treatments improved endothelial function of SHR through increasing NO participation and decreasing [image omitted] probably involving higher Cu/Zn-SOD expression. PLC treatment augmented eNOS expression in SHR. Surprisingly, LC increased [image omitted] produced by aorta from WKY and thus diminished NO and damaged endothelial function. Conversely, PLC did not affect CCh-induced relaxation in WKY. These results demonstrate that LC and PLC prevent endothelial dysfunction in SHR through an antioxidant effect.

摘要

为阐明左旋肉碱(LC)和丙酰左旋肉碱(PLC)对自发性高血压大鼠(SHR)和正常血压WKY大鼠抗氧化特性的潜在机制,用PLC或LC(200 mg·kg⁻¹)处理动物。解剖主动脉,在存在或不存在一氧化氮合酶(NOS)抑制剂L-NAME的情况下,评估对(R)-(-)-去氧肾上腺素(Phe)的收缩反应和对卡巴胆碱(CCh)的舒张反应。通过光泽精增强化学发光评估[图像省略]生成,并在用超氧化物歧化酶(SOD)加过氧化氢酶孵育后观察其对舒张的参与情况。通过蛋白质印迹法研究内皮型一氧化氮合酶(eNOS)、铜/锌超氧化物歧化酶(Cu/Zn-SOD)和锰超氧化物歧化酶(Mn-SOD)的蛋白表达。LC和PLC处理均通过增加NO参与和减少[图像省略]改善SHR的内皮功能,这可能涉及更高的Cu/Zn-SOD表达。PLC处理增加了SHR中eNOS的表达。令人惊讶的是,LC增加了WKY大鼠主动脉产生的[图像省略],从而减少了NO并损害了内皮功能。相反,PLC不影响WKY大鼠中CCh诱导的舒张。这些结果表明,LC和PLC通过抗氧化作用预防SHR的内皮功能障碍。

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