对氧磷酶1与多囊卵巢综合征的相关性研究

对氧磷酶(PON)是一类能催化水解磷酸酯键的芳香酯酶,能够水解高密度脂蛋白和低密度脂蛋白分子中的氧化型磷脂,具有抗氧化作用。PON活性异常与动脉粥样硬化发生密切相关,PON日益受到重视。随着临床和分子生物学的进展发现,PON的活性与多囊卵巢综合征及其并发症密切相关,但在国内尚未见报道。现就此研究进展作一综述。     

Antioxidant enzyme activities,lipid peroxidation,and total antioxidant status in children with Henoch–Schönlein purpura

The aim of this study was to assess the role of oxidative stress in the pathogenesis of Henoch–Schönlein purpura (HSP) vasculitis. The activities of catalase (CAT), arylesterase (ARYL), and paraoxonase (PON) as antioxidant enzymes and serum malondialdehyde (MDA) level as an indicator of lipid peroxidation, together with total antioxidant status (TAS), were measured in 29 children with HSP (mean age 9.3?±?2.7 years), both at the onset of the disease and at the remission period and in matched controls. Active-stage HSP had significantly higher MDA level (15.5?±?7.3 vs 7.8?±?3.9 nmol/l, respectively, P?P?P?=?0.042), ARYL (158?±?39 vs 212?±?52 U/l, P?P?=?0.002) activities compared with the control subjects. Although CAT (P?>?0.05) and PON (P?>?0.05) activities were found to be similar between active and remission stages of HSP, the active stage of the disease had significantly lower ARYL (P?=?0.011) and TAS (P?=?0.006) and higher MDA (P?r?=?0.433, P?=?0.019) and between CAT and C-reactive protein (r?=?0.386, P?=?0.035) in the active stage of HSP. No significant differences were detected in oxidant/antioxidant parameters between patients with or without renal, gastrointestinal, or joint involvement (P?>?0.05). Increased oxidative stress and lipid peroxidation may play important roles in the pathogenesis of HSP vasculitis. Antioxidant therapeutic interventions in long-lasting vasculitis and risk of atherosclerosis secondary to increased oxidant stress remain to be investigated.     

Lipid peroxidation markers in adult attention deficit hyperactivity disorder: New findings for oxidative stress

Malondialdehyde (MDA) is a reliable marker of lipid peroxidation where paraoxonase and arylesterase are two enzymes against it. Although increased MDA has been previously shown in adults with attention deficit/hyperactivity disorder (A-ADHD), levels of paraoxonase and arylesterase enzymes have not been studied yet. We aimed to determine the status of both MDA level and paraoxonase and arylesterase enzyme activities in A-ADHD patients. A total of 35 adults with ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria and 29 healthy volunteers were included in the study. Serum MDA, paraoxonase and arylesterase levels of the participants were measured. The disease severity of the patients was determined by using Turgay's Adult Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (ADD/ADHD) DSM IV Based Diagnostic Screening and Rating Scale. The serum MDA level of patients was significantly higher than that of healthy control subjects, whereas their paraoxonase and arylesterase levels were significantly lower. There was no correlation between the levels of biochemical parameters (MDA, paraoxonase and arylesterase) and the disease severity. Sub-types of A-ADHD were similar in terms of these biochemical parameters. Increased lipid peroxidation, a part of oxidative stress, in adults with ADHD appears to be unbuffered by antioxidant enzymes, namely paraoxonase and arylesterase.     

Paraoxonase and arylesterase activity and total oxidative/anti-oxidative status in patients with idiopathic Parkinson’s disease

This study investigated serum paraoxonase (PON1) and arylesterase activity along with determination of oxidative status via measurement of total oxidant status (TOS), total anti-oxidant status (TAS) and oxidative stress index (OSI) in patients with Parkinson’s disease (PD) and compared results with data from healthy controls. A total of 82 subjects, including 42 patients with idiopathic PD, newly diagnosed and untreated (24 men, 18 women, aged 47–66 years) and 40 healthy controls were enrolled in this study. We aimed to evaluate the oxidative status of PD patients via measurement of serum TOS and TAS and estimation of OSI using new automated methods. PON1 and arylesterase activities were measured spectrophotometrically. Serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels were measured using routine methods. TAS levels of PD patients were significantly lower than that of controls (p < 0.05). TOS levels of PD patients were higher than those of controls (p < 0.05). PON1 and arylesterase activities of PD were lower than those of controls (p < 0.05). Serum levels of total and LDL cholesterol were significantly reduced in PD patients. In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in PD patients supports the important role of oxidative stress in the pathophysiology of PD. Since oxidative stress is involved in neurodegeneration, selecting anti-oxidants, metal chelators or other compounds boosting endogenous enzymatic and non-enzymatic defense mechanisms seems to be an obvious choice as treatment for PD.     

髓过氧化物酶/对氧磷酶1与高密度脂蛋白功能的关系

目的 探讨冠心病患者髓过氧化物酶(MPO)/对氧磷酶1(PON1)与高密度脂蛋白（HDL）功能的关系及槲皮素对HDL功能的保护作用。方法 分别选取150名AMI和非冠心病住院患者,收集基本临床资料、生化指标及空腹静脉血,测定血浆中MPO和PON1的水平。培养人单核细胞（THP-1）,并诱导为巨噬细胞,分别用来源于AMI和非冠心病患者apoB缺乏的血清干预实验,测定胆固醇流出率、ABCA1和ABCG1蛋白和mRNA的表达、炎症因子TNF-α、IL-6的水平。结果 AMI组血浆中MPO水平明显高于非CHD组,PON1则明显低于非CHD组,两者比值MPO/PON1为AMI组小于非CHD组（P＜0.001）。4组间胆固醇流出率、ABCA1和ABCG1的蛋白及mRNA的表达、炎症因子TNF-α、IL-6水平的差异均有统计学意义。结论 AMI患者的HDL功能发生了改变,MPO/PON1水平可能间接反映HDL的胆固醇逆转运功能,槲皮素可以改善胆固醇的逆转运功能和巨噬细胞内的炎症反应。     

对氧磷酶1 55 Met/Leu、对氧磷酶2 148 Ala/Gly和锰超氧化物歧化酶9 Ala/Val基因多态性与冠心病

目的 探讨对氧磷酶155 Met/Leu(PON1 55 Met/Leu)、对氧磷酶2148 Ala/Gly(PON2148 Ala/Gly)和锰超氧化物歧化酶9 Ala/Val(MnSOD 9 Ala/Val)基因多态性与冠心病(CHD)、血浆对氧磷酶(PON)、总超氧化物歧化酶(T-SOD)和锰超氧化物歧化酶(MnSOD)活性以及丙二醛(MDA)浓度的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测262例CHD患者和100名对照组的PON1 55 Met/Leu、PON2 148 Ala/Gly和MnSOD 9 Ala/Val基因多态性的基因型,采用比色法测定血浆PON、T-SOD和MnSOD活性以及MDA浓度.结果 与对照组比较,CHD患者的血浆PON[(349.27±138.36 vs 454.75±166.00)nmol·min-1·ml-1,P＜0.001]、T-SOD[(23.61±16.51 vs.44.01±22.68)U/ml,P＜0.001]和MnSOD活性[(21.56±13.11 vs.28.79±8.65)U/ml,P＜0.001]明显降低,MDA浓度显著增高[(2.47±0.73 vs.2.15±0.55)nmol/ml,P＜0.01];CHD患者的PON1 55 LM杂合子基因型、M等位基因频率,PON2 148 GG纯合子基因型和AG杂合子基因型、G等位基因频率和MnSOD 9 AA基因型、A等位基因频率较对照组明显增多;PON1 55 LM杂合子基因型的PON和T-SOD活性较LL纯合子基因型明显降低;PON2 148GG基因型和AG基因型的PON活性较AA基因型明显降低;MnSOD AA基因型的PON和MnSOD活性较VV基因型明显降低;logistic回归分析显示PON1 55 LM杂合子基因型、M等位基因、PON2148 GG/AG基因型、G等位基因是CHD的危险因子.结论 CHD患者的抗氧化能力明显降低,脂质过氧化物显著增高;PON1 55 Met/Leu、PON2 148 Ala/Gly和MnSOD 9 Ala/Val基因多态性通过影响血浆PON和MnSOD活性而参与CHD的发病.     

脑梗死患者血清对氧磷酶基因192位点多态性检测

目的　建立检测脑卒中患者血清对氧磷酶 (Paraoxonase ,PON)基因 192位Arg/Glu多态性的简便实用方法。方法　碘化钠 (NaI)法提取外周血白细胞DNA ,应用多聚酶链反应 (PCR)对PON1基因酶切位点的限制性片段长度多态性 (RFLP)进行分析。结果　扩增产物经限制性内切酶消化后分别得到三种类型产物即 99bp一条带 ;33bp、6 6bp两条带 ;33bp、6 6bp、99bp三条带。所代表的PON1基因型分别为QQ型、RR型和QR型。结论　该检测方法对脑梗死患者具有简便、实用、特异性高、灵敏度好等优点 ,适于临床科研推广应用     

In vitro inhibitory effects of palonosetron hydrochloride,bevacizumab and cyclophosphamide on purified paraoxonase-I (hPON1) from human serum

In this study, we investigated the effects of the drugs, palonosetron hydrochloride, bevacizumab and cyclophosphamide, on human serum paraoxonase-I (hPON1) enzyme activity in in vitro conditions. The enzyme was purified ∼231-fold with 34.2% yield by using ammonium sulphate precipitation, DEAE-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel-filtration chromatography from human serum. hPON1 exhibited a single protein band on the SDS polyacrylamide gel electrophoresis. The inhibition studies were performed on paraoxonase activity of palonosetron hydrochloride, bevacizumab and cyclophosphamide. K_i constants were found as 0.033 ± 0.001, 0.054 ± 0.003 mM and 3.419 ± 0.518 mM, respectively. Compared to the inhibition rates of the drugs, palonosetron hydrochloride has the maximum inhibition rate. However, inhibition mechanisms of the drugs were determined as noncompetitive by Lineweaver-Burk curves.     

Time-dependent modulation of rat serum paraoxonase 1 activity by fasting

High-density lipoprotein-associated paraoxonase 1 (PON1) protects the endothelium from the pro-oxidant activity of oxidised low-density lipoprotein. Whereas fasting has been related to increased oxidative stress, intermittent fasting and caloric restriction are associated to increased resistance to oxidative injury. Taking into consideration that serum PON1 activity is modulated by a restriction of caloric intake and because there is no evidence regarding PON1 response to total food deprivation, we investigated whether PON1 activity is involved in the response aimed to counteract the greater oxidative stress associated to fasting and whether serum PON1 activity is altered by the length of food deprivation. Male Wistar rats were randomly divided into five groups: fed and 6-, 12-, 24- or 48-h fasted rats. Serum PON1 activity increases within the first hours of fasting, representing a prompt adaptation designed to attenuate blood lipid peroxidation that cannot be sustained when fasting is prolonged. This PON1 response to early fasting could be part of the mechanisms triggered by periodically repeated short periods of food deprivation—intermittent fasting—which result in increased resistance to stress by stimulating antioxidant defences.     

Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative stress

BackgroundIn this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1).MethodsPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography.ResultsThe calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors.ConclusionsOur results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC₅₀ values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K_i constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.