Kalogerakis George, Baker Arthur M, Christov Steve, Rowley Kevin G, Dwyer Karen, Winterbourn Christine, Best James D, Jenkins Alicia J
Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Fitzroy, 3065 Melbourne, Australia.
Clin Sci (Lond). 2005 Jun;108(6):497-506. doi: 10.1042/CS20040312.
In a cross-sectional study, oxidative stress in high vascular disease risk groups, ESRD (end-stage renal disease) and Type I diabetes, was assessed by measuring plasma protein carbonyls and comparing antioxidant capacity of HDL (high-density lipoprotein) as pertaining to PON1 (paraoxonase 1) activity and in vitro removal of LPO (lipid peroxides). ESRD subjects on haemodialysis (n=22), Type I diabetes subjects (n=20) without vascular complications and healthy subjects (n=23) were compared. Plasma protein carbonyls were higher in ESRD patients [0.16 (0.050) nmol/mg of protein; P=0.001; value is mean (SD)] relative to subjects with Type I diabetes [0.099 (0.014) nmol/mg of protein] and healthy subjects [0.093 (0.014) nmol/mg of protein]. Plasma PON1 activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PON1 activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PON1 activity and plasma protein carbonyl concentrations were inversely related (r=-0.50, P<0.05). In an in vitro assay, LPO removal by HDL in ESRD subjects was greater than HDL from healthy subjects (P<0.01), whereas HDL from patients with Type I diabetes was less effective (P<0.01). Efficacy of LPO removal was unrelated to plasma PON1 activity, in vitro glycation or mild oxidation, but was impaired by marked oxidation and glycoxidation. Protein carbonyl levels are increased in ESRD but not in complication-free Type I diabetes. HDL antioxidant function is increased in ESRD, perhaps a compensatory response to increased oxidative stress, but is lower in Type I diabetes. HDL dysfunction is related to glycoxidation rather than glycation or PON1 activity.
在一项横断面研究中，通过测量血浆蛋白羰基含量，并比较高密度脂蛋白（HDL）与对氧磷酶1（PON1）活性相关的抗氧化能力以及体外脂质过氧化物（LPO）清除能力，评估了高血管疾病风险组（终末期肾病，ESRD和I型糖尿病）的氧化应激情况。比较了接受血液透析的ESRD患者（n = 22）、无血管并发症的I型糖尿病患者（n = 20）和健康受试者（n = 23）。与I型糖尿病患者[0.099（0.014）nmol/mg蛋白质]和健康受试者[0.093（0.014）nmol/mg蛋白质]相比，ESRD患者的血浆蛋白羰基含量更高[0.16（0.050）nmol/mg蛋白质；P = 0.001；数值为均值（标准差）]。校正HDL胆固醇前后，糖尿病患者的血浆PON1活性均较低，但与健康受试者相比，ESRD患者的血浆PON1活性无差异。未校正HDL时，三组之间的血浆PON1活性无差异。在ESRD中，血浆PON1活性与血浆蛋白羰基浓度呈负相关（r = -0.50，P < 0.05）。在体外试验中，ESRD受试者的HDL对LPO的清除能力高于健康受试者的HDL（P < 0.01），而I型糖尿病患者的HDL清除效果较差（P < 0.01）。LPO清除效果与血浆PON1活性、体外糖基化或轻度氧化无关，但会因显著氧化和糖氧化而受损。ESRD患者的蛋白羰基水平升高，但无并发症的I型糖尿病患者则未升高。ESRD患者的HDL抗氧化功能增强，这可能是对氧化应激增加的一种代偿反应，但I型糖尿病患者的HDL抗氧化功能较低。HDL功能障碍与糖氧化有关，而非糖基化或PON1活性。
