Paraoxonase 1 (PON1) Q192R and L55M polymorphisms,lipid profile,lipid peroxidation and lipoprotein-a levels in Turkish patients with pregnancy-related disorders

Abstract

The aim of this study was to investigate the role of PON1Q192R and L55M single nucleotide polymorphisms(SNPs) and its association with the maternal levels of lipid parameters in gestational diabetes mellitus(GDM) and preeclampsia(PE). Ninety-nine pregnant with GDM, 97 pregnant with PE and 98 healthy pregnant were included in the study. No statistically significant difference was observed in the alleles or in the genotypes frequencies of SNPs between groups. In GDM patients, total cholesterol was higher in MM genotype of L55M gene (p?<?.05); Lp(a) were lower in LM genotype of the gene compared to their respective control (p?<?.05). In PE, HDL-C levels were higher in LM genotype (p?<?.05); LDL-C levels were lower in MM genotype of the gene compared to their respective control (p?<?.05). In PE patients, malondialdehyde(MDA) were higher in QQ genotype compared to their respective control (p?<?.05). Triglyceride levels were higher in PE patients with QR genotype compared with GDM patients with QR genotype (p?<?.05). Our results indicated that lipid profiles, Lp(a) and MDA levels showed significant differences in GDM and PE pregnants. These findings support the importance of the lipid profile, oxidized lipid and Lp(a) in different genotypes of L55M and Q192R in Turkish pregnant women with PE/GDM suggesting their roles in etiopathogenesis in these pregnancy-related disorders.     

脑络通胶囊对鹌鹑实验性动脉粥样硬化的预防作用

目的探讨脑络通胶囊抗动脉粥样硬化(AS)作用。方法制备鹌鹑AS模型 ,120只♂鹌鹑随机分为6组 :正常对照组、高脂对照组、月见草油丸组、脑络通大、中、小剂量组。结果脑络通可使鹌鹑升高的血脂(TC、TG、LDL_C和VLDL_C)水平进行性降低 ,(P<0.05、P<0.01) ,使HDL_C水平或HDL_C/TC值升高(P<0.05、P<0.01) ,并降低主动脉和心肌中TC、TG含量(P<0.05) ,对主动脉和冠状动脉内膜粥样斑块形成有明显的抑制作用(P<0.05、P<0.01)。结论脑络通有调脂作用和抗AS作用。     

依布硒啉对四氯化碳及内毒素+D-氨基半乳糖致肝损伤的保护作用

目的：考察依布硒啉(ebselen)对肝损伤的保护作用。方法：以0.2%四氯化碳(5 ml.kg^-1)和内毒素（1μg.kg^-1)+D-氨基半乳糖（800 mg.kg^-1)分别ip ICR小鼠形成肝损伤,观察病理改变及血清谷丙转氨酶(ALT)、总胆红素(TBIL)和总胆汁酸(TBA)活性。培养大鼠肝细胞以CCl₄和LPS＋D-GalN诱发损伤。测定了乳酸脱氢酶活性和细胞TBARS含量。结果：依伯硒啉可改善CCl₄和LPS＋D-GalN诱发的小鼠肝损伤变化,减小相关损伤指标的改变;并可拮抗培养肝细胞的LDH释放和TBARS含量上升。结论：依布硒啉能保护肝损伤,可能与抗自由基的脂质过氧化有关。     

Cyclosporine Transfer from Low- and High-Density Lipoproteins Is Partially Influenced by Lipid Transfer Protein I Triglyceride Transfer Activity

Purpose. The purpose of this study was to determine if lipid transfer protein (LTP I) facilitated triglyceride (TG) transfer activity regulates the plasma lipoprotein distribution of cyclosporine (CSA). Methods. To assess the influence of drug concentration and incubation time on the plasma lipoprotein distribution of CSA, ³H-CSA (50 to 1000 ng/ml) was incubated in human plasma for 5 to 120 minutes at 37°C. To determine if LTP I facilitated TG transfer activity regulates the plasma lipoprotein distribution of CSA, ³H-Triolein (TG)- or ³H-CSA-enriched high-density lipoproteins (HDL) or low-density lipoproteins (LDL) were incubated in T150 buffer (50 mM Tris-HCl, 150 mM NaCl, 0.02% Sodium Azide, 0.01% Disodium EDTA), pH 7.4 which contained a ³H-Triolein (TG) or ³H-CSA-free lipoprotein counterpart ± exogenous LTP I (1.0 g protein/ml) or in delipidated human plasma which contained 1.0 g protein/ml of endogenous LTP I for 90 minutes at 37°C. These experiments were repeated in the presence of a monoclonal antibody TP1 (15 g protein/ml) directed against LTP I. Results. No differences in CSA lipoprotein distribution were observed following incubation of the drug at varying concentrations and incubation times in human plasma. The percent transfer of TG from HDL to LDL and LDL to HDL was greater in T150 buffer than in human plasma. However, the percent transfer of CSA from only LDL to HDL was greater in T150 buffer than in human plasma. Furthermore, undetectable ³H-CSA transfer from HDL to LDL in T150 buffer containing purified LTP I was observed. In addition, when the percent transfer of TG and CSA were determined in the presence of TP1, the percent transfer of TG and CSA from only LDL to HDL were significantly decreased in T150 buffer and human plasma compared to controls. Conclusions. These findings suggest that the transfer of CSA between different lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.     

Lipid Association Increases the Potency Against Primary Medulloblastoma Cells and Systemic Exposure of l-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU) in Rats

Purpose. To reduce the systemic toxicity and prolong the systemic presence of l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU), a lipid-based drug carrier was designed and characterized. Methods. The degree of CCNU association with lipid vesicles composed of 1,2-dimyristoyl-sn- glycero-3-phosphocholine (DMPC) and l,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) (1:1, m/m) was characterized and the drug decomposition rates of lipid-drug complexes were monitored. Effects of lipid association on drug potency against medulloblastoma cells and total systemic drug exposure in rats were determined. Results. At a CCNU:lipid molar ratio greater than 1:5, more than 90% of the drug was associated with the lipid vesicles. In aqueous suspensions, lipid association significantly reduced the first-order drug decomposition rate. In addition, lipid-associated CCNU exhibited a 4-fold increase in drug sensitivity with medulloblastoma cells. IC₅₀ values for CCNU admixed and encapsulated with lipid vesicles were 18 ± 4.9 and 14.0 ± 2.2 M, respectively, compared to 83 ± 11.0 M for free CCNU. When administered to rats, lipid-associated CCNU increased the AUC (area under the concentration-time curve) of CCNU by approximately 2-fold (20.46 ± 2.15 compared to 39.59 ±1.87 gmin/ml), and the terminal half-life (t_1/2) by almost 9-fold (17 ± 9 compared to 147 ± 48 min) over free CCNU. Despite the increase in total systemic drug exposure, rats treated with lipid-associated CCNU exhibited a significantly lower frequency of acute neurotoxicity. Conclusions. These data indicate that CCNU associated with lipid vesicles may increase drug stability, potency, and systemic exposure in rats.     

几种香茶菜属二萜化合物对自由基导致线粒体损伤的保护作用

目的了解香茶菜属二萜类化合物冬凌草甲素（Ｏｒｉｄ）、腺花香茶素（Ａｄｅ）、黄花香茶菜素（Ｓｃｕｌ）是否具有抗氧化作用。方法用分光光度法测定脂质过氧化物丙二醛（ＭＤＡ）含量及线粒体肿胀度。用荧光分光光度法测定线粒体膜流动性。结果Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ４０,８０,１６０μｍｏｌ·Ｌ－１抑制铁－半胱氨酸（Ｆｅ２＋－Ｃｙｓ）引起的肝线粒体ＭＤＡ形成,并呈剂量依赖关系。Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ１６０μｍｏｌ·Ｌ－１抑制肝线粒体膜流动性下降（Ｐ值分别为２．２９７±０．０２２,０．３８９±０．００９,０．３８２±０．０１３,Ｆｅ２＋－Ｃｙｓ的Ｐ值为０．４２３±０．０１４）;Ａｄｅ１６０μｍｏｌ·Ｌ－１还可抑制脂质过氧化引起的肝线粒体肿胀。结论Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ可能通过抑制脂质过氧化而产生抗氧化作用     

总丹酚酸的抗脑缺血研究

目的探讨总丹酚酸对脑缺血的影响及其相关机制。方法脑缺血模型采用ＭＣＡＯ,离体测定总丹酚酸对脂质过氧化、超氧阴离子、羟自由基的作用。结果发现在ＭＣＡＯ模型上,总丹酚酸１２５～２５ｍｇ·ｋｇ－１有缩小脑梗塞面积、减轻脑水肿之功效,离体研究发现,总丹酚酸抗氧化作用极为明显,５～５０ｍｇ·Ｌ－１时可抗Ｆｅ２＋ 半胱氨酸诱导的肝微粒体脂质过氧化、清除黄嘌呤 黄嘌呤氧化酶体系产生的超氧阴离子、清除Ｆｅ２＋ Ｈ２Ｏ２体系产生的羟自由基作用,且同等剂量下均强于对照药ＶｉｔＥ。结论总丹酚酸有抗脑缺血作用,机制与抗氧化有关。     

虎杖有效成分3,4′,5-三羟基芪-3-β-D-葡萄糖苷的研究进展

总结了虎杖有效成分3,4′,5-三羟基芪-3-β-D-葡萄糖苷(虎杖晶Ⅳ) 近10年来的研究,评价了虎杖晶Ⅳ在防止动脉内皮损伤性血栓形成,改善休克微循环,提高休克大鼠存活率,减轻缺血再灌注,自由基,内毒素等造成的组织器官损伤,降血脂及抗脂质过氧化等方面的作用. 提示虎杖晶Ⅳ可能成为治疗血栓性疾病及改善休克微循环等方面一个有特色的新药.     

山莨菪碱对红细胞自氧化的影响

目的　研究山莨菪碱（Ａｎｉ）在红细胞自氧化损伤中的作用。方法　在红细胞悬液中加入不同浓度Ａｎｉ,温育２４ｈ,分别用比色法、硫代巴比妥酸荧光法、荧光偏振法测定红细胞溶血度、红细胞膜脂质过氧化物（ＬＰＯ） 、红细胞膜微粘度。结果　Ａｎｉ１－０,１－５ ｍ ｍｏｌ·Ｌ－１ 可显著抑制红细胞自氧化溶血（ 溶血度分别为：０－５８５ ±０－０２８、０－４３９ ±０－０２４,对照组为０－７９８ ±０－０３５ ,Ｐ＜０－０１）、显著降低红细胞膜ＬＰＯ〔分别为：（０－３５９ ±０－０１７） 、（０－３２３ ±０－０１９）μｍｏｌ·ｇ－１ Ｐｒｏ,对照组为（０－４１８±０－０１５）μｍｏｌ·ｇ－１ Ｐｒｏ, Ｐ＜ ０－０１〕、显著降低红细胞膜微粘度〔分别为：（０－３２８±０－０１７）、（０－２９６ ±０－０１９）Ｐａ·ｓ,对照组为（０－３７４ ±０－０１４） Ｐａ·ｓ〕。结论　Ａｎｉ 抗氧自由基引发的膜脂质过氧化、保护细胞膜,对红细胞自氧化损伤有保护作用     

4-氧和4-羟四甲基哌啶氮氧自由基及衍生物抗脂质过氧化作用研究

 目的:对6种四甲基哌啶氮氧自由基及衍生物(4-TEMPO)抗脂质过氧化作用进行了实验研究,为其进一步研究及应用于临床作为抗自由基损伤药物提供依据。方法:用Fe²⁺-VitC引发大鼠肝细胞膜、心肌细胞膜、肝线粒体的脂质过氧化,通过TAB比色法测定丙二醛(MDA)含量观测了4-TEMPO抗脂质过氧化作用。结果:OTMPO(4-氧-2,2,6,6-四甲基哌啶氮氧自由基)、HTMPO(4-羟-2,2,6,6-四甲基哌啶氮氧自由基)、HTMPOH(4-羟-2,2,6,6-四甲基羟哌啶)、OTMPOH(4-氧-2,2,6,6-四甲基羟哌啶)有较强的剂量依赖性抑制MDA产生的作用,且OTMPOH,HTMPOH较OTMPO,HTMPO作用强,而OTMP(4-氧-2,2,6,6-四甲基哌啶)、HTMP(4-羟-2,2,6,6-四甲基哌啶)无效。结论:4-TEMPO有较明显的对抗脂质过氧化作用,作为一种临床抗自由基引起的脂质过氧化损伤的药物研究及开发利用,可能有广泛的前景。