Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy

Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy
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DOI:
10.1007/s10238-009-0084-7
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发表时间:
2010-09-01
影响因子:
4.6
通讯作者:
Nowak, Katarzyna
Nowak, Katarzyna
中科院分区:
医学3区
文献类型:
--
作者:
Nowak, Mariusz;Wielkoszynski, Tomasz;Nowak, Katarzyna

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本研究的目的是评价1型糖尿病患者血清铁还原能力(FRAS)、对氧磷酶1(PON 1)、铜蓝蛋白血清氧化酶活性和hsCRP水平。本研究在76例1型糖尿病患者中进行,35例无糖尿病视网膜病变(第1组)和41例增殖前和增殖性视网膜病变(第2组)。对照组为35名年龄、性别、体质量相匹配的非糖尿病健康志愿者,在门诊进行常规健康体检。我们使用Benzie和Strain描述的方法评价FRAS;使用对氧磷作为底物通过动力学分光光度法测定PON 1,使用血浆铜蓝蛋白以3-苯二胺作为底物的氧化活性。采用高灵敏度酶免疫法测定CRP。糖尿病视网膜病变患者的PON 1活性(227.66 +/- A 123.57 U/l)显著低于对照组(312.04 +/- A 129.77 U/l)。与第1组(522.79 +/- A 167.56 μ mol/l)和对照组(529.80 +/- A 81.99 μ mol/l)相比,第2组(439.33 +/- A 79.87 μ mol/l)的FRAS显著降低。与对照组(45.22 +/- A 14.96 U/g蛋白)相比,第1组铜蓝蛋白活性(58.36 +/- A 22.56 U/g蛋白)显著升高。我们发现,与第1组(1.75 +/- A 1.01 mg/l)和对照组(0.57 +/- A 0.46 mg/l)相比,第2组(3.71 +/- A 2.47 mg/l)的hsCRP水平显著升高。对照组的PON 1/CRP比值与糖尿病患者相比明显升高,第2组与第1组相比明显降低。在对照组和研究组中,我们没有发现研究参数的性别依赖性差异。我们发现老年患者的血清FRAS和hsCRP活性有降低的趋势,但仅在第2组中差异显着。FRAS和PON 1活性在伴有糖尿病视网膜病变的1型糖尿病患者中降低,这证实氧化应激在糖尿病视网膜病变的发病机制中可能起作用。与无糖尿病视网膜病变的患者相比,存在糖尿病视网膜病变的糖尿病患者中hsCRP水平显著升高,这提供了炎症与糖尿病微血管并发症发生之间的联系。由于PON 1/CRP比值在无糖尿病视网膜病变和有糖尿病视网膜病变的患者之间存在显著差异,因此PON 1:CRP比值似乎可用作视网膜病变进展的生化标志物。抗氧化剂浓度,炎症和糖尿病并发症的发展之间的联系需要进一步的纵向研究,以证实我们的发现。
The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 +/- A 123.57 U/l) when compared with control (312.04 +/- A 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 +/- A 79.87 mu mol/l) when compared with group 1 (522.79 +/- A 167.56 mu mol/l) and control (529.80 +/- A 81.99 mu mol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 +/- A 22.56 U/g protein) when compared with control (45.22 +/- A 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 +/- A 2.47 mg/l) when compared with group 1 (1.75 +/- A 1.01 mg/l) and control (0.57 +/- A 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.