Liver growth factor treatment reverses vascular and plasmatic oxidative stress in spontaneously hypertensive rats
Liver growth factor treatment reverses vascular and plasmatic oxidative stress in spontaneously hypertensive rats
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DOI：
10.1097/hjh.0b013e328353824b
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发表时间：
2012-06-01
影响因子：
4.9
通讯作者：
Carmen Gonzalez, M.
中科院分区：
文献类型：
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作者：
Condezo-Hoyos, Luis;Arribas, Silvia M.;Carmen Gonzalez, M.
背景：肝生长因子（LGF）是一种体外具有抗氧化作用的白蛋白-胆红素复合物。在自发性高血压大鼠（SHRs）中，短时间LGF治疗具有抗高血压和抗纤维化作用。方法：以Wistar-Kyoto （WKY）为对照菌株，观察LGF治疗（4次腹腔注射，4.5 μ g/大鼠，12 d）是否能降低SHRs的氧化应激。我们评估了以下内容：血浆氧化应激生物标志物[蛋白结合丙二醛（MDA）；蛋白质羰基和晚期糖基化终产物[AGEs]；双氢乙醚共聚焦显微镜检测颈动脉源性血管平滑肌细胞（VSMCs）超氧阴离子基底生成；颈动脉内NADPH、黄嘌呤氧化酶、CuZn、Mn、细胞外超氧化物歧化酶（sod）和过氧化氢酶的表达（western blot）和活性（波谱法）。结果：LGF治疗可逆转SHRs血浆MDA、蛋白羰基和VSMC超氧阴离子水平升高，对WKY菌株无影响；逆转了SHR血管p22phox表达以及NADPH氧化酶、黄嘌呤氧化酶和过氧化氢酶活性的变化；对血管中CuZn-SOD和Mn-SOD表达及总SOD活性无影响；逆转SHR血管糖基化/游离细胞外sod表达比和血浆葡萄糖的升高，而血浆AGEs未发生变化。结论：LGF治疗SHRs可通过降低血管中NADPH和黄嘌呤氧化酶产生的超氧阴离子，使血浆氧化应激生物标志物水平正常化。这些作用可能与LGF的心血管再生作用有关。
Background: Liver growth factor (LGF) is an albumin-bilirubin complex with antioxidant actions in vitro. In spontaneously hypertensive rats (SHRs), short LGF treatment exerts antihypertensive and antifibrotic effects.Method: We aimed to determine if LGF treatment (4 i.p. injections, 4.5 mu g/rat over 12 days) reduces oxidative stress in SHRs using Wistar-Kyoto (WKY) as control strain. We assessed the following: plasma oxidative stress biomarkers [protein-bound malondialdehyde (MDA); protein carbonyls and advanced glycation end products (AGEs)]; superoxide anion basal production in carotid artery-derived vascular smooth muscle cells (VSMCs) detected by dihydroethidium and confocal microscopy; and expression (western blot) and activities (spectroscopic methods) of NADPH and xanthine oxidases, CuZn, Mn and extracellular superoxide dismutases (SODs) and catalase in carotid arteries.Results: LGF treatment had the following effects: reversed the increase in plasma MDA and protein carbonyls and VSMC superoxide anion levels observed in SHRs, without any effect on WKY strain; reversed the alterations in SHR vascular p22phox expression as well as NADPH oxidase, xanthine oxidase and catalase activities; had no effect on vascular CuZn-SOD and Mn-SOD expression or total SOD activity; and reversed the elevation in SHR vascular glycated/free extracellular-SOD expression ratio and plasma glucose without changes in plasma AGEs.Conclusion: LGF treatment of SHRs normalizes the level of plasma oxidative stress biomarkers through a reduction of vascular superoxide anion produced by NADPH and xanthine oxidases. These effects might be linked to the cardiovascular regenerative actions of LGF.