氧化低密度脂蛋白在慢性梗阻性黄疸大鼠肝脏中的表达与意义

目的 探讨氧化低密度脂蛋白在慢性梗阻性黄疸大鼠中的表达与肝脏纤维化的关系.方法 60只SD大鼠被随机分成对照组（A组）和慢性梗阻性黄疸组（B组）两组,每组每时段6只.分别于造模后第1、2、3、4、5周抽取大鼠静脉血检查肝功能,显微镜目镜刻度下测量大鼠胆总管直径,免疫荧光法检测氧化低密度脂蛋白在肝脏的表达,放射免疫法检测肝纤维化三项,光学显微镜观察肝组织的病理改变.第4周行胆总管十二指肠吻合再通.结果 慢性梗阻性黄疸组大鼠术后总胆红素升高,胆总管直径扩张,组织病理学检查显示肝细胞变性,并有纤维增生性改变.与对照组比较,慢性梗阻性黄疸组肝组织氧化低密度脂蛋白的表达增强,肝纤维化三项术后第3周起明显升高.胆总管与十二指肠端侧吻合再通后黄疸缓慢消退.术后第3周氧化低密度脂蛋白的表达及肝纤维化三项差异有统计学意义（P 〈 0.05）.结论 慢性梗阻性黄疸大鼠肝组织氧化低密度脂蛋白的表达增强,与肝脏的纤维化的程度相关.     

Ox-LDL increases OX40L in endothelial cells through a LOX-1-dependent mechanism

Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of atherosclerosis, and it can stimulate the expression of a variety of inflammatory signals. As a new and highly sensitive inflammation index, OX40L may be a key to understanding the mechanisms that regulate interactions between cells within the vessel wall and inflammatory mediators during the development of atherosclerosis. To investigate whether Ox-LDL regulates OX40L expression through an oxidized LDL-1 receptor (LOX-1)-mediated mechanism, we investigated the effect of different concentrations of Ox-LDL (50, 100, 150 µg/mL) on endothelial cell proliferation and apoptosis. Stimulation with Ox-LDL increased OX40L protein 1.44-fold and mRNA 4.0-fold in endothelial cells, and these effects were inhibited by blocking LOX-1. These results indicate that LOX-1 plays an important role in the chronic inflammatory process in blood vessel walls. Inhibiting LOX-1 may reduce blood vessel inflammation and provide a therapeutic option to limit atherosclerosis progression.     

氧化低密度脂蛋白对人脐静脉内皮细胞PECAM-1基因转录的影响

目的探讨氧化低密度脂蛋白（Ox-LDL）对人血管内皮细胞血小板内皮细胞黏附分子-1（PECAM-1）mRNA表达的影响。方法体外培养人脐静脉内皮细胞（HUVEC），采用铜离子氧化24h制备Ox-LDL。取HUVEC以100mg／LOx-LDL分别孵育0．5、1、1．5、2h，另取HUVEC分别用100 mg／LLDL和0、50、100、200mg／LOx-LDL孵育1．5h．均采用RT-PCR技术检测细胞中PECAM-1基因的转录水平。结果Ox-LDL除正常LDL所含成分外．还含有胆固醇亚油酸酯的过氧化特异斑点X和甲基脂肪酸。Ox-LDL作用0．5h时PECAM-1 mRNA表达水平最低；随时间延长，表达水平逐渐升高，与0．5h时比较，P〈0．05；至2h时．PECAM-1表达水平有所回落，但与0．5h时比较，P-〈0．05。0、50、100、200mg／LOx-LDL作用1．5h，PECAM-1表达水平逐渐升高，以100mg／L时表达水平最高。100mg／LLDL作用1.5h时，PECAM-1表达水平无明显变化。结论Ox-LDL可在转录水平上调血管内皮细胞PECAM-1基因表达．从而促进血管内皮细胞高水平表达PECAM-1。     

Both Atorvastatin and Probucol Can Down-regulate BMP-2 Expression Induced by Oxidized Low Density Lipoprotein in Human Umbilical Vein Cells

Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.     

不同剂量的阿托伐他汀对ACS患者ox-LDL的影响

目的探讨不同剂量的阿托伐他汀对急性冠脉综合症(ACS)患者血浆氧化型低密度脂蛋白(ox-LDL)及超敏C-反应蛋白(hs-CRP)的影响。方法以120例经临床症状和/或冠脉造影确定为ACS的患者为研究对象,根据阿托伐他汀剂量的不同随机分为阿托伐他汀常规剂量组(20 mg/d,60例)和阿托伐他汀大剂量组(40 mg/d,60例),分别于入院24 h内及服药后1周、2周测定两组患者的ox-LDL及hs-CRP水平,并进行比较。结果治疗前、治疗后1周、治疗后2周两组的ox-LDL水平分别为[常规剂量组:(0.62±0.12)mg/L,(0.47±0.14)mg/L,(0.33±0.13)mg/L;大剂量组:(0.63±0.15)mg/L,(0.41±0.11)mg/L,(0.21±0.15)mg/L];两组的hs-CRP水平为[常规组:(17.62±1.90)mg/L,(8.81±2.6)mg/L,(6.22±0.87)mg/L;大剂量组:(17.81±2.42)mg/L,(7.24±3.82)mg/L,(3.88±0.81)mg/L]。治疗前两组的ox-LDL及hs-CRP差异无统计学意义(P>0.05),治疗后1周、2周二者的水平较治疗前均明显下降(P<0.01),但是大剂量组下降水平较常规治疗组更显著(P<0.05)。结论大剂量的阿托伐他汀能更有效降低ACS患者的ox-LDL及hs-CRP的水平。     

抗氧化剂对Ox—LDL诱导内皮细胞Bcl-2蛋白表达的影响

目的　探讨抗氧化剂Se和VitE对Ox -LDL诱导体外培养的牛主动脉内皮细胞Bcl -2蛋白的影响。　方法　Ox -LDL与VitE、Se处理牛主动脉内皮细胞后 ,通过流式细胞仪和DNA电泳检测细胞凋亡 ,采用Westernblot检测Bcl -2蛋白表达。　结果　Ox -LDL作用内皮细胞后 ,DNA电泳呈明显梯度条带 :加入Se和VitE后 ,内皮细胞平均凋亡率较Ox -LDL组明显降低 (P <0 .0 5 ) ,Westernblot检测Bcl -2蛋白表达明显增加 (P <0 .0 5 )。　结论　Se和VitE能减少Ox -LDL诱导体外培养的牛主动脉内皮细胞凋亡 ,其作用机制与上调Bcl -2蛋白表达有关     

Low-energy cranberry juice decreases lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 ± 0.6 to 2.2 ± 0.4 μmol/L [means ± SD], P < .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 ± 31.0 to 80.4 ± 34.6 U/L and 3.4 ± 1.1 to 1.7 ± 0.7 μmol/L, respectively [means ± SD], P < .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome.     

Loxin polymorphism is associated with increased resistin levels and with oxidative status

Objectives

We hypothesized that LOX-1 polymorphism may impact on inflammation and cardiovascular risk by modulating systemic resistin expression.

Design and methods

276 men were randomly selected from a population-based cohort. Metabolic and inflammatory markers were evaluated at baseline and after 6-years follow-up, OLR1 (loxin) IVS4-14 A>G polymorphism was assessed.

Results

Mean plasma resistin and nitrotyrosine values were significantly higher, and TAS was significantly lowered in homozygous for the G allele. The G allele was significantly and directly associated with resistin and nitrotyrosine values.

Conclusion

Enhanced oxidized-LDL uptake by LOX-1 G-allele carriers is associated with increased pro-oxidant status and resistin levels, suggesting a major uptake of ox-LDL by macrophages, smooth muscle cells, and monocytes.