阿托伐他汀抑制血管内皮细胞氧化应激反应的研究

目的:以不同浓度的阿托伐他汀干预内皮细胞的氧化应激反应,借助8一Is叩和MDA这两个检测指标衡量阿托伐他汀的抗氧化能力。方法:设立对照组的同时分组给予不同浓度的阿托伐他汀干预,再以氧化型低密度脂蛋白处理人脐静脉内皮细胞,最后提取细胞培养上清液,分别以ELISA法和硫代巴比妥酸法检测8-Isop和MDA的含量。结果:阿托伐他汀对8-Isop和MDA的产生有影响,且有浓度依赖性的趋势;抑制8-Isop和抑制MDA的程度无显著性差异。结论:阿托伐他汀有一定的抗氧化应激能力,并呈剂量依赖性。     

阿托伐他汀抗动脉粥样硬化的研究进展

<正>阿托伐他汀是一种羟甲基戊二酸单酰辅酶A(HMGCoA)还原酶抑制剂,1978年在美国诞生后被广泛应用于临床脂类疾病的治疗,可降低血浆总胆固醇和低密度脂蛋白胆固醇(LDL-C),并影响机体炎症反应、血管内皮功能、血栓形成等病理生理过程,在调节抗动脉粥样硬化、减少急性心脑血管事件的发生方面发挥着重要作用。现就阿托伐他汀抗动脉硬化的研究进展综述如下。1药代动力学阿托伐他汀是3-羟基3-甲基戊二酰辅酶A(HMG-CoA)     

瑞舒伐他汀对兔动脉粥样硬化斑块及血清PAPP-A的影响

目的:探讨瑞舒伐他汀对兔动脉粥样硬化斑块及血清妊娠相关血浆蛋白(PAPP-A)的影响.方法:新西兰家兔18只,随机分为正常对照组(Normal组,n=6)、动物粥样梗化模型组(AS组,n=6)和瑞舒伐他汀治疗组(RSV组,n=6).于治疗前、治疗后,检测血清总胆固醇(TC)、三酰甘油(TG)、血清低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)含量,酶联免疲吸附法(ELISA)检测血清PAPP-A水平.同时,用血管内超声检查(IVUS)测定病变部位的血管外弹力膜面积(EEMA)、管腔面积(LA)和斑块面积(PA),计算管腔面积狭窄百分率(LAS%).结果:治疗前,AS组和RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较Normal组高(P<0.01),HDL-C的水平较Normal组低(P<0.01);治疗后,RSV组兔的血清TC、TG、LDL-C及PAPP-A比AS组低(P<0.01).HDL-C的水平比AS组高(P<0.01),且RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较治疗前低(P<0.01),HDL-C的水平较治疗前高(P<0.01).血管内超声检查结果显示,治疗后,RSV组兔的LAS%(30.87%±5.27%)比AS组低(37.42%±6.12%)(P<0.01).结论:瑞舒伐他汀能改善对AS兔血脂,减少AS斑块形成及降低血清PAPP-A水平.     

川穹内酯联合阿托伐他汀对VCAM-1和PAI-1的抑制作用和抗动脉粥样硬化作用研究

目的:分析川穹内酯联合阿托伐他汀对VCAM-1和PAI-1的抑制作用,并研究两类药物联用对抗动脉粥样硬化的意义。方法:以2010年5月-2013年5月间于我院接受治疗的198例动脉粥样硬化为研究对象,以随机数字表法将其划分为观察组和对照组;对照组患者在常规保守治疗的基础上联用阿托伐他汀;观察组在对照组的基础上联用川穹内酯。对比治疗前后VCAM-1和PAI-1的血清浓度变化,统计血液生化检测及超声动脉检测结果。结果:1治疗后,两组患者两指标均上升,检测发现观察组VCAM-1和PAI-1明显低于对照组,组间差异具备统计学意义(P0.05)。2TC、LDL-C、HDL-C及颈动脉IMT和斑块Crous积分的变化均显示,观察组各指标改善情况明显优于对照组,对比差异均显著(P0.05)。结论:以川穹内酯联合阿托伐他汀;可有效抑制VCAM-1和PAI-1的表达;提升动脉粥样硬化治疗效果。     

不同剂量阿伐他汀联合阿司匹林治疗原发性高血压并动脉粥样硬化的临床研究

目的:探讨不同剂量阿托伐他汀联合阿司匹林治疗原发性高血压并动脉粥样硬化的临床疗效。方法:选取2015年1月-2016年12月在我院治疗的原发性高血压并动脉粥样硬化患者80例,随机分为对照组和实验组,每组40例。实验组给予口服高剂量阿托伐他汀(40 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗,对照组给予口服高剂量阿托伐他汀(20 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗,疗程均为3个月。观察和比较两组患者治疗前后的总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high-density lipoproteincholesterol,HDL-C)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、收缩压(systolic blood pressure,SBP)、舒张血压(diastolic blood pressure,DBP)以及颈动脉斑块分级。结果:两组治疗后的SBP、DBP、血清TC、TG和LDL-C水平均较治疗前显著降低,血清HDL-C水平较治疗前明显升高,且实验组SBP、DBP、血清TC、TG和LDL-C水平均显著低于对照组(P0.05),血清HDL-C水平明显高于对照组(P0.05)。实验组颈动脉斑块0-Ⅰ级的比例显著高于对照组(P0.05)。结论:口服高剂量阿托伐他汀(40 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗原发性高血压并动脉粥样硬化较低剂量阿托伐他汀(20 mg/d)联合阿司匹林肠溶片(100 mg/d)疗效更好,可以有效降低血压,调节血脂并改善患者预后。     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的：观察他汀类调脂药物瑞舒伐他汀（Rosuvastatin）对2型糖尿病（type2diabetesmellitus,T2DM）大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法：将45只雄性SD大鼠随机分为正常对照组（NC组）、2型糖尿病组（DM组）、2型糖尿病瑞舒伐他汀治疗组（DR组）,每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/（kg.d）灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）水平与稳态血糖（BG）、稳态胰岛素（PGI）浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40（clusterofdifferentiation 40,CD40）及基质金属蛋白酶-2（MMP-2）、激活蛋白-1（activator protein-1,AP-1）的表达水平。结果：DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高（F=33.71~426.05,q=5.26~40.82,P〈0.01）,但2组间各指标比较差异无显著性（P〉0.05）。DR组CD40、MMP-2、AP-1表达水平和浸润的单核细胞数明显低于DM组（F=36.86~716.82,q=8.59~37.86,P〈0.05）,DR组主动脉内皮损伤明显轻于DM组。结论：瑞舒伐他汀能抑制CD40、MMP-2、AP-1表达和单核细胞浸润,防止早期AS形成。     

RP-HPLC法测定阿托伐他汀在新西兰兔体内的药代动力学

目的:研究阿托伐他汀片在新西兰兔体内的药代动力学.方法:18只成年健康雄性新西兰兔.随机分为正常对照组、10mg/kg·d阿托伐他汀片组与15 mg/kg·d阿托伐他汀片组,每组6只,采用RP-HPLC法测定血药浓度,计算药代动力学参数.结果:10mg/kg·d组与15 mg/kg·d组的主要药代动力学参数分别为:AUC0～t/μ g·L-1·h为(619.58±215.45)与(1138.34±422.32)、AUC0～∞/μ g·L-1·h为(655.68±242.83)与(1216.57±353.64)、Cmax/μ g·L-1为(455.81±168.52)和(896.53±168.5.8)、MRT0～t/h为(3.68±0.75)与(5.73±0.56)、MRT0～∞/h为(3.83±0.91)与(5.25±0.48)、Tmax/h为(2.51±0.82)与(3.68±0.33)、T1/2/h为(4.22±0.55)与(9.51±0.67).结论:RP-HPLC法适用于阿托伐他汀片动物药代动力学的研究.     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的:观察他汀类调脂药物瑞舒伐他汀(Rosuvastatin)对2型糖尿病(type2diabetesmellitus,T2DM)大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法:将45只雄性SD大鼠随机分为正常对照组(NC组)、2型糖尿病组(DM组)、2型糖尿病瑞舒伐他汀治疗组(DR组),每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/(kg.d)灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平与稳态血糖(BG)、稳态胰岛素(PGI)浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40(clusterofdifferentiation 40,CD40)及基质金属蛋白酶-2(MMP-2)、激活蛋白-1(activator protein-1,AP-1)的表达水平。结果:DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高(F=33.71~426....     

瑞舒伐他汀对OX-LDL诱导的人脐静脉内皮细胞PPAR-gamma表达的影响

目的：探讨经氧化低密度脂蛋白（OX-LDL）刺激后,人脐静脉内皮细胞（PPAR-gamma）表达的变化,以及瑞舒伐他汀对动脉粥样硬 化的影响。方法：将实验标本随机分为2 组,分为（OX-LDL）刺激组、瑞舒伐他汀干预组。应用RT-PCR及Western blot 技术,观察 OX-LDL 诱导的人脐静脉内皮细胞PPAR-gamma表达情况及瑞舒伐他汀对人脐静脉内皮细胞PPAR-gamma及浓度依赖的方式降低了人脐静脉内皮细胞PPAR-gamma的表达;2）瑞舒伐他汀可以逆转OX-LDL 对人脐静脉内细胞的影响 并可能与甲羟戊酸有关。结论：OX-LDL可降低人脐静脉内皮细胞PPAR-gamma的表达。瑞舒伐他汀可以抑制OX-LDL诱导人脐静脉 内皮细胞PPAR-gamma表达的增强,从而可能抑制了OX-LDL信号通路介导的与炎症有关的血管损伤,延缓动脉粥样硬化的进程。     

阿托伐他汀治疗对肾脏衰老的影响

目的：观察长期应用不同剂量的阿托伐他汀对老年大鼠肾脏的影响。方法：正常20月龄Wistar雌性大鼠分为3组（n=9）：①给予大剂量阿托伐他汀10 mg/（kg.d）灌胃;②给予小剂量阿托伐他汀1 mg/（kg.d）灌胃;③给予等剂量生理盐水灌胃,三组均连续灌胃4个月后处死大鼠,以3月龄大鼠（n=9）为对照。测定肾重指数,血清肌酐及血清脂蛋白,行PAS染色、天狼猩红染色观察肾脏病理,计算肾小球硬化指数。结果：三组老年大鼠的肾脏重量均显著减轻。老年大鼠小剂量阿托伐他汀组显著降低老年大鼠的血清肌酐（P〈0.01）。老年大鼠血脂水平显著高于青年大鼠,大剂量阿托伐他汀组显著降低老年大鼠的总胆固醇（CH）和低密度脂蛋白胆固醇（LDL-C,P均〈0.05）,小剂量阿托伐他汀组显著降低老年大鼠的LDL-C（P〈0.05）。大剂量阿托伐他汀组降低血脂的作用强于小剂量阿托伐他汀组。老年大鼠肾脏病理改变为显著的肾小球局灶节段性硬化,肾小球硬化指数显著增高（P〈0.05）,肾间质内大量炎性细胞浸润,肾内小动脉明显硬化。阿托伐他汀组显著减轻肾小球的局灶节段性硬化的程度,减少肾间质内炎性细胞浸润,显著改善肾内小动脉粥样硬化的病变程度。大剂量阿托伐他汀改善肾组织异常病理表现的作用更为明显。结论：长期应用阿托伐他汀可以显著改善老年大鼠肾脏衰老的异常病理改变,这些作用可能是通过阿托伐他汀的降脂作用、显著减轻肾内小动脉硬化及显著减少肾间质内炎性细胞浸润而综合起效的。     

Radiation-induced changes in the cell membrane of cultured human endothelial cells

We investigated the effect of irradiation on the kinetic characteristics of amino acid and glucose transport, and the effect on the activity of the cell membrane-bound enzyme 5'-nucleotidase and on the receptor-mediated stimulation of cyclic adenosine monophosphate synthesis by prostaglandin E1. Irradiation inhibited the sodium-dependent amino acid transport by a reduced binding of the amino acid to the transport unit. The transport of glucose, which appeared to be a sodium-independent process, was temporarily stimulated by increased maximal velocity of the transport. No effect was found on the binding to the transport unit. Irradiation increased the 5'-nucleotidase activity and decreased the prostaglandin E1-stimulated cyclic adenosine monophosphate synthesis 48 h after exposure to 20 Gy. It is concluded that irradiation decreases sodium-dependent transport by impairment of the transport unit, does not impair a sodium-independent process, and has opposite effects on membrane-bound enzyme activity and a receptor-mediated process.     

Linking irradiance-induced changes in pit membrane ultrastructure with xylem vulnerability to cavitation

The effect of shading on xylem hydraulic traits and xylem anatomy was studied in hybrid poplar (Populus trichocarpa x deltoides, clone H11-11). Hydraulic measurements conducted on stem segments of 3-month-old saplings grown in shaded (SH) or control light (C) conditions indicated that shading resulted in more vulnerable and less efficient xylem. Air is thought to enter vessels through pores in inter-vessel pit membranes, thereby nucleating cavitation. Therefore, we tested if the ultrastructure and/or chemistry of pit membranes differed in SH and C plants. Transmission electron micrographs revealed that pit membranes were thinner in SH, which was paralleled by lower compound middle lamella thickness. Immunolabelling with JIM5 and JIM7 monoclonal antibodies surprisingly indicated that pectic homogalacturonans were not present in the mature pit membrane regardless of the light treatment. Porosity measurements conducted with scanning electron microscopy were significantly affected by the method used for sample dehydration. Drying through a gradual ethanol series seems to be a better alternative to drying directly from a hydrated state for pit membrane observations in poplar. Scanning electron microscopy based estimates of pit membrane porosity probably overestimated real porosity as suggested by the results from the 'rare pit' model.     

Lipid peroxidation and endothelial cell injury: implications in atherosclerosis

Vascular endothelial cells, which play an active role in the physiological processes of vessel tone regulation and vascular permeability, form a border separating deeper layers of the blood vessel wall and cellular interstitial space from the blood and circulating cells. Damage or dysfunction of endothelial cells may reduce the effectiveness of the endothelium to act as a selectively permeable barrier to plasma components, including cholesterol-rich lipoprotein remnants. This may be involved in the etiology of atherosclerosis. Experimental evidence indicates that free radical-mediated lipid peroxidation can induce endothelial cell injury/dysfunction. Reactive oxygen species, including peroxidized lipids capable of initiating cell injury, may be generated within endothelial cells, be present in plasma components, or be derived from neutrophils or other blood-borne cells. Lipid peroxidation could initiate or promote the process of atherosclerotic lesion formation by directly damaging endothelial cells, and by enhancing the adhesion and activation of neutrophils and the susceptibility of platelets to aggregate. Endothelial cell injury by lipid hydroperoxides also could increase the uptake of LDL into the vessel wall. These events and other cellular dysfunctions may individually or collectively initiate and/or help to sustain the development of atherosclerosis.     

Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis

The endothelium is a key constituent of the vascular wall, being actively involved in maintaining the structural integrity and proper functioning of blood vessels. Hyperlipidemia, diabetes, hypertension, smoking and aging are important risk factors for the dysfunction of endothelial cells (EC). Circulating lipoproteins (Lp) synthesized and secreted from the intestine or liver have an important role in supplying peripheral tissues with fatty acids from triglyceride rich lipoproteins (TGRLp) for energy production or storage, and cholesterol from low density lipoproteins (LDL) or high density lipoproteins (HDL) for the synthesis of cellular membranes and steroid hormones. Under pathological conditions, Lp may suffer alterations in concentration and composition and become aggressors for EC. Modified LDL, remnant Lp, TGRLp lipolysis products, dysfunctional HDL are involved in the changes induced in EC morphology (reduced glycocalyx, overdeveloped endoplasmic reticulum, Golgi apparatus and basement membrane), loose intercellular junctions, increased oxidative and inflammatory stress, nitric oxide/redox imbalance, excess Lp transport and storage, as well as loss of anti-thrombotic properties, all of these being characteristics of endothelial dysfunction. Normal HDL are able to counteract the harmful effects of atherogenic Lp in EC but under persistent pathological conditions they lose the protective properties and become pro-atherogenic. This review summarises recent advances in understanding the role of Lp in the induction of endothelial dysfunction and the initiation and progression of atherosclerotic lesions. Its main focus is the antagonistic role of atherogenic Lp (LDL, VLDL, dysfunctional HDL) versus anti-atherogenic Lp (HDL), also pointing out the potential targets for arresting or reversing this process.     

大蒜酒对家兔实验性动脉硬化模型血液流变学的影响

动脉硬化与血液流变学的关系日益受到重视.近年来的研究发现, 在动脉粥样硬化斑形成尤其在造成动脉管壁内皮细胞损伤过程中,血液这种流体所具有的流变性也发生相应变化.大蒜具有抗AS的作用早有报道,而大蒜在抗AS过程中对血液流变性的影响却未见报道.我们以大蒜为主要原料研制大蒜酒,观察其对AS模型家兔血液流变性的影响,现报道如下. 1 材料与方法 1.1 大蒜酒:以大蒜为主要原料,用特殊配方和工艺研制大蒜酒,既去除大蒜的异味,又具有酒的芳香.     

The ultrastructure of the oyster brown cell,a cell with a fenestrated plasma membrane

Summary The oyster brown cell, a connective tissue cell of uncertain function and affinity, was characterized in the electron microscope by (1) the presence of large cytoplasmic granules, (2) fenestrations of the plasma membrane, and (3) an extensive tubular network originating in, or emptying into, the plasma membrane fenestrations. The brown cell did not appear to be a cell involved in glycogen storage or in the manufacture of exportable protein. The extensive tubular network and the membrane slits suggested that the brown cell may have been involved in the processing of biological fluids.This work was supported in part by Public Health Service Contract No. 5 To 1 ES00038-02, Health Sciences Advancement Award No. RR06138, and Tumor Biology Training Grant, NIH CA 05245.We wish to thank Miss Grete Nilsen for her expert technical assistance and Mr. Bob Munn for his help in the use of the electron microscope and for proof reading our MS. Our appreciation is also extended to Dr. J. Luft, Dr. A. K. Sparks, Miss P. Phelps, Mr. M. DeVault, and to the personnel of the Johnson Oyster Company, Inverness.     

Dynamic changes of red cell membrane thiol groups followed by bimane fluorescent labeling

Monobromobimane labels red cell membrane protein thiol groups; bands exhibit fluorescence after sodium dodecyl sulfate acrylamide gel electrophoresis and correspond to almost all of those staining with Coomassie blue. The response of membrane protein thiol groups to oxidative challenge and the dynamics of recovery of the thiol groups may be followed. Diminished labeling is found after oxidation with diamide, with both intrachain and interchain disulfide bond formation demonstrated by sodium dodecyl sulfate acrylamide gel electrophoresis. Regeneration of thiol groups under physiological conditions (incubation with glucose) after a moderate degree of diamide oxidation is shown to be complete (with respect to thiol group content and degree and distribution of bimane label) in normal human red blood cell membranes. Even after oxidation of almost half of the membrane protein thiol groups (maximum degree of oxidation achieved), regeneration of thiol groups is almost complete; a minor fraction resides in the form of disulfide-linked high molecular weight proteins (demonstrated by the electrophoretic profile) which may be reduced completely with dithiothreitol.Bimane fluorescent labeling provides a convenient and sensitive method for following membrane thiol group status under physiological conditions.     

Smooth muscle and endothelial cell function in the pathogenesis of atherosclerosis.

Although clinical studies have been very useful in identifying factors that accelerate the development of atherosclerotic vascular disease, the pathogenesis of the vascular lesions remains unknown. Studies carried out in the last 10 years have shown that smooth muscle and endothelial cells of the vascular wall play a very important role in atherogenesis. It has become apparent that these cells are very active metabolically during the initiation and subsequent growth of the plaques, and that the materials that these cells produce and secrete are important in the composition and growth of the plaques. In addition, there are important interactions at the vessel wall-blood interface that involve endothelial cells, hemodynamic forces and many constituents of the blood, including platelets, lipoproteins, coagulation factors, fibrinolytic agents and leukocytes. In this article the numerous functions of both smooth muscle and endothelial cells are discussed and the effects of known atherogenic agents on these cellular functions are reviewed. Emphasis is placed on the important interactions that take place both within the vessel wall and at the vessel wall-blood interface. Understanding of the regulation of smooth muscle and endothelial cell function during the development and subsequent growth of fibrofatty plaques may be useful in designing appropriate therapeutic interventions to control atherosclerotic disease.     

Concurrent changes in Dunaliella salina ultrastructure and membrane phospholipid metabolism after hyperosmotic shock

Hyperosmotic shock, induced by raising the NaCl concentration of Dunaliella salina medium from 1.71 to 3.42 M, elicited a rapid decrease of nearly one-third in whole cell volume and in the volume of intracellular organelles. The decrease in cell volume was accompanied by plasmalemma infolding without overall loss of surface area. This contrasts with the dramatic increase in plasmalemma surface area after hypoosmotic shock (Maeda, M., and G. A. Thompson. 1986. J. Cell Biol. 102:289-297). Although plasmalemma surface area remained constant after hyperosmotic shock, the nucleus, chloroplast, and mitochondria lost membrane surface area, apparently through membrane fusion with the endoplasmic reticulum. Thus the endoplasmic reticulum serves as a reservoir for excess membrane during hyperosmotic stress, reversing its role as membrane donor to the same organelles during hypoosmotically induced cell expansion. Hyperosmotic shock also induced rapid changes in phospholipid metabolism. The mass of phosphatidic acid dropped to 56% of control and that of phosphatidylinositol 4,5-bisphosphate rose to 130% of control within 4 min. Further analysis demonstrated that within 10 min after hyperosmotic shock, there was 2.5-fold increase in phosphatidylcholine turnover, a twofold increase in lysophosphatidylcholine mass, a four-fold increase in lysophosphatidate mass, and an elevation in free fatty acids to 124% of control, all observations suggesting activation of phospholipase A. The observed biophysical and biochemical phenomena are likely to be causally interrelated in providing mechanisms for successful accommodation to such severe osmotic extremes.