基因敲除动脉粥样硬化小鼠模型研究进展

基因敲除小鼠动脉粥样硬化模型是目前较为认可的探讨动脉粥样硬化发病机制及寻找新药物靶点的关键工具,也应用于潜在抗动脉粥样硬化药物的药理和毒理研究。载脂蛋白E(ApoE)、低密度脂蛋白受体(LDLR)和B类Ⅰ型清道夫受体(SR-B1)等基因的表达促进机体脂质、胆固醇和低密度脂蛋白等转运和代谢,维持血管正常功能,敲除这些基因会引起脂质转运及代谢紊乱从而诱发动脉粥样硬化及并发症的发生发展。常见的基因敲除小鼠有ApoE基因敲除、LDLR基因敲除及其改良品系,这些模型小鼠能够客观反映敲除基因对动脉粥样硬化发生的影响,且广泛应用于动脉粥样硬化的非临床研究。本文阐述了当前基因敲除小鼠动脉粥样硬化模型的机制、应用和优缺点,以期为动脉粥样硬化发病机制研究及抗动脉粥样硬化药物筛选提供参考。     

硫化氢供体对Apo E基因敲除小鼠动脉粥样硬化的调节作用

目的探讨硫化氢(H2S)供体对Apo E基因敲除小鼠(Apo E-/-)动脉粥样硬化的调节作用。方法6wk龄正常C57BL/6J和Apo E-/-小鼠分为正常对照组、ApoE-/-组和Apo E-/-+硫氢化钠(NaHS)组,每组各8只,普通饮食饲养至16wk龄。分别观察各组小鼠血清中总胆固醇(TCHO)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)含量及主动脉根部斑块面积的变化;用硫电极法测定血清中H2S的含量。结果与对照组相比,Apo E-/-小鼠血清中TCHO[(12.59±3.11vs2.32±0.40)μmol·L-1]和LDL-C[(1.33±0.43vs0.13±0.03)μmol·L-1]水平明显升高,而HDL-C水平[(0.45±0.13vs1.49±0.21)μmol·L-1]明显降低,血清中H2S的含量[(44.64±4.52)μmol·L-1]较对照组[(57.69±7.03)μmol·L-1]明显下降,主动脉根部明显出现斑块[(139316.6±30362.93vs0)μm2];给予NaHS后,Apo E-/-小鼠血清中TCHO、LDL-C和HDL-C水平无明显变化,而血清中H2S的含量明显升高[(52.21±7.24vs44.64±4.52)μmol·L-1],主动脉根部动脉粥样硬化斑块明显缩小[(85927.84±1922.73vs139316.6±30362.93)μm2]。结论新型气体信号分子H2S可以延缓动脉粥样硬化的进程,缩小动脉粥样硬化斑块形成。     

ApoE-/-小鼠在中医抗动脉粥样硬化研究中的应用及进展

<正>在全球范围内,心血管疾病已成为威胁人类健康的“头号杀手”,而动脉粥样硬化(atherosclerosis, AS)是心血管疾病共同的病理生理基础,已成为欧美国家第一大死亡原因;在中国,随着经济水平及生活方式的改变,其发病率也呈逐年上升趋势。ApoE-/-小鼠由美国洛克菲勒大学生化遗传与代谢实验室和北卡罗莱纳大学病理遗传实验室应用胚胎干细胞基因敲除技术于1992年培育成功。ApoE-/-小鼠是动脉粥样硬化研究的经典动物模型,     

复方总黄酮对ApoE基因敲除小鼠动脉粥样硬化的影响

目的探讨复方总黄酮对ApoE基因敲除小鼠动脉粥样硬化的保护作用。方法 15只7周龄的♂C57BL/6小鼠普通饮食为正常对照组;75只7周龄的♂ApoE基因敲除小鼠高脂饮食,随机分为5组:模型组、辛伐他汀组、低剂量复方总黄酮组、中剂量复方总黄酮组、大剂量复方总黄酮组。灌胃16周造模完成后,采集血清,分离胸主动脉。HE染色检查胸主动脉斑块,检测血脂4项(TC、TG、LDL-C、HDL-C)和血清SOD;ELISA检测IL-1β、NF-κB值。结果模型组胸主动脉斑块明显,复方总黄酮组斑块均不同程度变小。复方总黄酮组的TC、TG、LDL-C、IL-1β、NF-κB明显降低,HDL-C、SOD含量明显升高,与模型组比较差异有显著性(P<0.05)。结论复方总黄酮对小鼠早期动脉粥样硬化有良好的保护作用,可能与其降脂抗炎作用有关。     

银杏内酯B对ApoE基因敲除小鼠动脉粥样硬化的影响

目的探讨银杏内酯B(ginkgolide B,GB)对ApoE基因敲除(ApoE-/-)小鼠动脉粥样硬化的影响。方法 12只8周龄C57BL/6J小鼠为正常组,24只8周龄♂ApoE-/-小鼠为阳性模型组以及药物组;药物组每天给予GB 0.6 mg灌胃。8周后处死小鼠,用病理学方法观察小鼠动脉斑块、脂质沉积以及巨噬细胞表达。用ELISA方法测定血浆RAN-TES含量。结果电镜结果显示模型组动脉斑块较大,血管内膜损伤明显,而GB组小鼠动脉内表面损伤明显减轻,斑块较小。HE染色显示了同样的结果,模型组斑块较大,GB组斑块较小。血浆RANTES测定正常组为123.81 ng.L-1,模型组为359.16 ng.L-1,GB组为193.36 ng.L-1,各组之间差异存在统计学意义(P<0.01)。结论 GB能有效地减轻ApoE-/-小鼠的动脉粥样硬化损伤,并降低血浆RANTES含量,其药理学机制可能与抑制血小板功能相关。     

芍药苷抗ApoE基因缺失小鼠动脉粥样硬化作用的初步研究

目的:探讨芍药苷(paeoniflorin,PF)对ApoE(apolipoprotein E,载脂蛋白E)基因缺失(ApoE^-/-)小鼠动脉粥样硬化的作用。方法:采用紫外可见分光光度法测定体外芍药苷的抗氧化能力包括还原力、过氧化自由基清除能力以及DPPH自由基清除能力。18只雄性ApoE^-/-小鼠随机分为芍药苷组和生理盐水组,ApoE^-/-小鼠高脂喂养8周,于第6周开始灌胃给予60 mg·kg^-1芍药苷,qd,持续8周。小鼠眼眶取血,分离血浆,检测小鼠血浆中总胆固醇(TC),三酰甘油(TG)、游离胆固醇(FC)以及SOD水平。小鼠脱臼处死后分离胸腹主动脉,油红O染色检测胸腹主动脉的脂质沉积。结果:0.2 mg·ml^-1维生素C甲醇溶液与32 mg·ml^-1芍药苷甲醇溶液的还原力相当,随着剂量增加芍药苷还原力升高。DPPH自由基清除力也随着剂量增加而增加,其中,0.8 mg·ml^-1芍药苷甲醇溶液具有约50% DPPH自由基清除力。同时, 4 mg·ml^-1芍药苷甲醇溶液具有约50%过氧化自由基清除力。动物实验研究结果表明:芍药苷组小鼠血浆SOD水平升高26.9%,与生理盐水组比较,差异显著(P<0.01)。60 mg·kg^-1芍药苷显著降低小鼠血浆中TC和TG水平(P<0.05),但对血浆中FC水平作用不明显。与生理盐水组比较,芍药苷组腹主动脉脂质沉积显著减少(P<0.05)。结论:芍药苷可延缓ApoE^-/-小鼠动脉粥样硬化的发展,其机制可能与其抗氧化及降低血脂水平有关。     

优降脂组方对ApoE基因敲除动脉粥样硬化模型小鼠的动脉粥样硬化相关细胞因子的影响

目的 探讨优降脂组方对ApoE基因敲除（ApoE-/-）动脉粥样硬化模型小鼠的动脉粥样硬化相关细胞因子的影响。方法 选择ApoE-/-小鼠45只,同时选择同遗传背景C57BL/6J小鼠雄性15只。造模成功后分为4组：模型组、正常对照组、优降脂组方实验组、阿托伐他汀对照组。实验结束后,测定4组小鼠血脂水平及动脉粥样硬化相关细胞因子水平。结果 模型组小鼠TC、TG、LDL-C均高于正常对照组,HDL-C低于正常对照组,差异有统计学意义（P<0.05）。优降脂组方实验组和阿托伐他汀对照组TC、TG、LDL-C均低于模型组,HDL-C均高于模型组,差异有统计学意义（P<0.05）。模型组小鼠hs-CRP、TNF-α、MDA均高于正常对照组,NO低于正常对照组,差异有统计学意义（P<0.05）。优降脂组方实验组和阿托伐他汀对照组hs-CRP、TNF-α、MDA均低于模型组,NO均高于模型组,差异有统计学意义（P<0.05）。结论 优降脂组方有助于降低血脂水平,对动脉粥样硬化发生和发展有一定抑制作用,为临床提供一定的实验理论依据。     

Caveolin-1在载脂蛋白E基因敲除小鼠动脉粥样硬化形成中的变化

目的：探讨caveolin-1在apoE基因敲除小鼠动脉粥样硬化形成过程中的变化。方法：取正常和apoE基因敲除小鼠(品系均为C57BL／6J)作为研究对象，分别观察不同周龄apoE基因敲除小鼠血清甘油三酯、总胆固醇、低密度脂蛋白、高密度脂蛋白的含量及主动脉横断面积、斑块面积的变化。免疫组织化学染色法对caveolin-1进行半定量及定位分析，Western-blotting检测caveolin-1在主动脉的表达。结果：apoE基因敲除小鼠的血清甘油三酯、总胆固醇、低密度脂蛋白水平与对照组比较显著升高，并随小鼠周龄增加而升高；斑块面积及斑块面积与主动脉面积的比值也随小鼠周龄增加而增大。免疫组织化学染色法显示，caveolin-1在实验组血管内膜表达呈阳性减弱，其程度随周龄增加有减少趋势。免疫印迹检测显示实验组caveolin-1的表达与对照组比较有所减弱，并与小鼠周龄呈负相关。结论：apoE基因敲除小鼠主动脉内皮细胞caveolin-1表达下调，可能与其动脉粥样硬化形成有关。     

白鲜皮水提物对ApoE-/-小鼠动脉粥样硬化晚期病变形成的影响

目的研究白鲜皮水提物(cortex dictamni aqueous extract,CDAE)对载脂蛋白E基因缺损小鼠主动脉弓粥样硬化晚期病变形成的影响及其机制。方法将40只ApoE-/-小鼠随机分成空白对照组和CDAE高、中、低3剂量组(CDAE3.2、1.6、0.8 g·kg-1),每组10只。从第12周龄开始给药至18周龄。实验结束时测定给药前后总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平。取各组小鼠主动脉弓,OCT包埋,每只小鼠制作80张病理切片(厚6μm),计算各组主动脉弓粥样硬化病变的面积。体外实验测定CDAE给药后平滑肌细胞的增殖和迁移能力。结果CDAE给药后可明显减少动脉粥样硬化斑块面积,CDAE中、高剂量组给药后ApoE-/-小鼠动脉粥样硬化病变面积均小于对照组(P<0.05,P<0.01),各给药组血脂水平均有不同程度的下降。体外实验表明,CDAE可明显抑制大鼠血管平滑肌细胞的增殖和PDGF诱导的平滑肌细胞迁移。结论CDAE对ApoE-/-小鼠动脉粥样硬化晚期病变形成具有明显的抑制作用,其作用机制可能与降低血脂水平,抑制平滑肌细胞的增殖和迁移能力有关。     

利拉鲁肽对ApoE基因缺陷小鼠动脉粥样硬化及相关危险因素的影响

目的观察长效胰高糖素样肽-1类似物利拉鲁肽对Apo E基因缺陷小鼠动脉粥样硬化及相关血清学指标的影响。方法高脂饲料喂养Apo E基因缺陷小鼠诱导动脉粥样硬化形成,并随机分为对照组(不给药,n=11)和利拉鲁肽组(30μg·d-1,皮下注射,共4周,n=12)。比较两组小鼠主动脉粥样硬化斑块面积/管腔面积、内膜厚度/中膜厚度、血脂、血清一氧化氮(NO)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)水平。结果对照组和利拉鲁肽组小鼠斑块面积/管腔面积、内膜厚度/中膜厚度无显著差异(P>0.05),两组中体重增加在中位数以下的小鼠进行亚组比较,利拉鲁肽组斑块面积/管腔面积、内膜厚度/中膜厚度均显著下降(P<0.05)。利拉鲁肽组总胆固醇、三酰甘油、低密度脂蛋白胆固醇、TNF-α水平显著低于对照组(P<0.05),NO水平显著高于对照组(P<0.05),两组间MDA水平无显著差异(P>0.05)。结论利拉鲁肽具有减轻体重、改善血脂水平,保护内皮功能及抑制炎症反应等作用,并可能通过减轻体重发挥潜在的抗动脉粥样硬化作用。     

Beijing ambient particle exposure accelerates atherosclerosis in ApoE knockout mice

Background

Air pollution is associated with significant adverse health effects including increased cardiovascular morbidity and mortality. However research on the cardiovascular effect of “real-world” exposure to ambient particulate matter (PM) in susceptible animal model is very limited. In this study, we aimed to investigate the association between Beijing ambient particle exposure and the atherosclerosis development in the apolipoprotein E knockout mice (ApoE^−/− mice).

Methods

Two parallel exposure chambers were used for whole body exposure among ApoE knockout mice. One of the chambers was supplied with untreated ambient air (PM group) and the other chamber was treated with ambient air filtered by high-efficiency particulate air (HEPA) filter (FA group). Twenty mice were divided into two groups and exposed to ambient PM (n = 10 for PM group) or filtered air (n = 10 for FA group) for two months from January 18th to March 18th, 2010. During the exposure, the mass concentrations of PM_2.5 and PM₁₀ in the two chambers were continuously monitored. Additionally, a receptor source apportionment model of chemical mass balance using 19 organic tracers was applied to determine the contributions of sources on the PM_2.5 in terms of natural gas, diesel vehicle, gasoline vehicle, coal burning, vegetable debris, biomass burning and cooking. At the end of the two-month exposure, biomarkers of oxidative stress, inflammation and lipid metabolism in bronchoalveolar lavage fluid (BAL) and blood samples were determined and the plaque area on the aortic endothelium was quantified.

Results

In the experiment, the concentrations of PM₁₀ and PM_2.5 in PM chamber were 99.45 μg/m³ and 61.0 μg/m³ respectively, while PM_2.5 in FA chamber was 17.6 μg/m³. Source apportionment analysis by organic tracers showed that gasoline vehicle (39.9%) and coal burning (24.3%) emission were the two major sources contributing to the mass concentration of PM_2.5 in Beijing. Among the ApoE knockout mice, the PM group were significantly higher than the FA group in terms of serum total cholesterol, low-density lipoprotein, tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein as well as TNF-alpha and interleukin-6 in BAL. Also the total antioxidant capacity and oxidized low-density lipoprotein were significantly different between the two groups. In addition, pathological analysis of aortic arch reveals that the plaques area in the PM group increased significantly compared to the FA group.

Conclusions

Our results demonstrated that ambient PM exposure could induce considerable oxidative stress and systemic inflammation in ApoE knockout mice and contribute to the progression of atherosclerosis.     

Protective effect of artemisinin on chronic alcohol induced-liver damage in mice

The liver disease related to chronic alcohol consumption is one of the leading causes of death for alcoholics. The efficient drug to ameliorate the alcoholic liver injury was needed urgently. The present study was performed to investigate whether artemisinin possessed the protective effect against chronic alcohol consumption. 50 male Kunming mice were divided into 5 groups: control group (C): 10 ml/kg saline + 10 ml/kg saline, alcohol group (A): 10 ml/kg 56%(v/v) alcohol + 10 ml/kg saline, low dose group of artemisinin (L): 10 ml/kg 56%(v/v) alcohol + 30 mg/kg/day artemisinin, medium dose group of artemisinin (M): 10 ml/kg 56%(v/v) alcohol + 60 mg/kg/day artemisinin, high dose group of artemisinin (H): 10 ml/kg 56%(v/v) alcohol + 120 mg/kg/day artemisinin. Drugs were given orally every day. The general state of mice was observed and the levels of serum activities of AST and ALT were detected after treatment with drugs for 30 days. Besides, the liver weight index was calculated and histopathological analysis was performed. We successfully demonstrated that treatment with high dose of artemisinin significantly decreased the elevated levels of AST (p < 0.05) and ALT (p < 0.01) in plasma, as well as the liver weight index (p < 0.01). The loss of body weight, tissue injury, oedema and inflammatory cell infiltration in the hepatocytes were found in the A group. These symptoms were remarkably alleviated in animals treated with artemisinin. Artemisinin can inhibit the activation of NF-кB and the expression of inflammatory cytokines inducible nitric oxide synthase. Besides, it can also enhance the stability of liver cell membrane, and reduce the damage of liver cell membrane and liver cell. Artemisinin showed a protective effect against chronic alcohol poisoning and it has a great potential for the clinical application to treat the liver injury induced by alcohol.     

Rosiglitazone promotes atherosclerotic plaque stability in fat-fed ApoE-knockout mice

Type 2 diabetes is considered a "risk equivalent" for cardiovascular disease, rosiglitazone, as an insulin sensitizer, has been explored as a novel therapeutic drug for the prevention of cardiovascular disease, but whether it can stabilize vulnerable atherosclerotic plaques is still unknown. Our study aims to investigate the effect of rosiglitazone on plaque stability in fat-fed ApoE-knockout mice. Our findings showed that rosiglitazone can stabilize the vulnerable atherosclerotic plaques in fat-fed ApoE-knockout mice by modifying the plaque composition as well as decreasing the number of buried fibrous caps and its anti-inflammatory effect probably is the key mechanism through which promotes the plaque more stable.     

从青蒿素的残膏中再提青蒿素的方法

目的 研究开发从分离青蒿素后的废弃残膏中再提取、纯化青蒿素的工艺路线.方法 采用萃取-结晶法.结果 可从残膏中再提取、纯化青蒿素,平均收率为0.86%,纯度为95.75%.结论 成功地建立了从青蒿素的残膏中再提取青蒿素的方法,该方法简便、收率高,具有一定的应用价值.     

抗炎抗凝融合蛋白TAP-SSL5对ApoE基因敲除小鼠动脉粥样硬化病变形成的影响

摘 要 目的：探讨重组融合蛋白蜱抗凝血肽（TAP） 金黄色葡萄球菌超抗原样蛋白5（SSL5）对ApoE基因敲除（ApoE-/-）小鼠动脉粥样硬化病变形成的影响。方法: 选取12周龄雄性ApoE-/-小鼠21只,随机分为3组：TAP-SSL5组（3 mg·kg^-1·d^-1）、SSL5组（2 mg·kg^-1·d^-1）、空白对照组（pH 7.4磷酸盐缓冲液）,ip,qd,连续给药12周,观察小鼠体质量变化。高脂饮食饲养12周后取材,检测血浆总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;对小鼠主动脉血管进行石蜡切片,常规HE染色,分析小鼠主动脉根部血管动脉粥样硬化斑块的形成情况,小鼠主动脉内膜面采用油红O染色,比较动脉粥样硬化斑块的分布情况。结果: 高脂饲养12周后,与空白对照组比较,TAP-SSL5组小鼠体质量增长和TC水平明显降低（P<0.001）,而TG、HDL-C、LDL-C水平无明显变化。HE染色结果表明,TAP-SSL5组主动脉根部切片斑块面积明显降低（P<0.05）;主动脉大体标本斑块油红O染色提示TAP-SSL5干预组主动脉动脉粥样硬化斑块形成明显小于空白对照组。结论:TAP-SSL5可显著抑制ApoE-/-小鼠动脉血管粥样硬化斑块的形成。     

青蒿素类衍生物抗肿瘤研究进展

青蒿素类药物是很好的抗疟药物,近年来大量体内、外研究显示青蒿素具有良好的抗肿瘤活性。大多数肿瘤细胞表面有高浓度的转铁蛋白受体,因此与正常细胞相比,细胞内含有更多的亚铁离子,青蒿素与亚铁离子反应生成自由基,可以选择性的杀伤肿瘤细胞。G1期细胞的转铁蛋白受体表达和铁离子摄入都显著增多,青蒿素类药物在此期诱导细胞凋亡,其具体作用靶点和机制还有待进一步研究,青蒿素衍生物还具有抗肿瘤血管生成活性。将青蒿素类药物与转铁蛋白上的糖基共价结合的复合体,可以将铁离子和青蒿素同时摄入肿瘤细胞,增强了青蒿素的高效性和靶向性。     

青蒿素及其衍生物药理作用研究有关进展

青蒿素属倍半萜内酯化合物,其衍生物主要有双氢青蒿素、青蒿琥酯、蒿甲醚和蒿乙醚,现在临床上主要用于治疗疟疾。随着对青蒿素及其衍生物药理作用的研究不断深入,除抗疟作用外,近年来又相继报道了抗炎、抗细菌脓毒症、抗肿瘤、放射增敏、抗菌增敏、抗组织纤维化等作用。笔者在此对国内外近年发现的青蒿素及其衍生物药理作用研究的最新现状作一综述。     

Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice

Non-selective inhibition of cyclooxygenase (COX) has been reported to reduce atherosclerosis in both rabbit and murine models. In contrast, selective inhibition of COX-2 has been shown to suppress early atherosclerosis in LDL-receptor null mice but not more advanced lesions in apoE deficient (apoE(-/-)) mice. We investigated the efficacy of the novel COX inhibitor indomethacin phenethylamide (INDO-PA) on the development of different stages of atherosclerotic lesion formation in female apoE(-/-) mice. INDO-PA, which is highly selective for COX-2 in vitro, reduced platelet thromboxane production by 61% in vivo, indicating partial inhibition of COX-1 in vivo. Treatment of female apoE(-/-) mice with 5mg/kg INDO-PA significantly reduced early to intermediate aortic atherosclerotic lesion formation (44 and 53%, respectively) in both the aortic sinus and aorta en face compared to controls. Interestingly, there was no difference in the extent of atherosclerosis in the proximal aorta in apoE(-/-) mice treated from 11 to 21 weeks of age with INDO-PA, yet there was a striking (76%) reduction in lesion size by en face analysis in these mice. These studies demonstrate the ability of non-selective COX inhibition with INDO-PA to reduce early to intermediate atherosclerotic lesion formation in apoE(-/-) mice, supporting a role for anti-inflammatory approaches in the prevention of atherosclerosis.     

硅胶柱层析纯化青蒿素

目的确定硅胶柱层析对超临界CO2萃取所得青蒿素粗品纯化的工艺条件。方法采用薄层层析-硅胶柱层析法考察不同展开剂的层析效果,最优洗脱剂为正己烷-乙醚(80∶20);以青蒿素回收率和平均含量为评价指标,考察了流速、进样量与层析柱再生条件对层析分离的影响。结果硅胶柱层析纯化青蒿素的最佳操作条件为洗脱剂空塔流速0.5cm.min-1,进样量18.9mg.ml-1柱体积,甲醇再生2倍床层体积。青蒿素含量可由原来的15%提高到70%以上,回收率达90%。经过重结晶精制,产品中青蒿素含量超过99.5%。结论硅胶柱层析纯化青蒿素所得产品符合质量要求。     

普伐他汀对鼠动脉粥样硬化及炎症因子的影响

目的 研究普伐他汀对鼠动脉粥样硬化形成过程及炎症因子的影响.方法 取40只大鼠制作动脉粥样硬化模型,随机分为正常饮食组（A）、对照组（B）、普伐他汀（C,10mg＆#183;kg-1＆#183;d-1）、普伐他汀（D,20mg＆#183;kg-1＆#183;d-1）各10只.B、C、D组定期腹腔注射维生素D破坏内皮细胞,喂养3个月,抽血检测hs-CRP,IL-6,并解剖大鼠制作病理切片,最后处死所有大鼠.结果 B组病理切片显示内膜明显增厚,管壁弥漫性隆起,内皮下含大量泡沫细胞,中膜平滑肌细胞增生.而A组内膜光滑,内皮下未见泡沫细胞,中膜平滑肌排列整齐有序,未见增生改变,C、D组内膜增生情况较B组轻,较A组重,且C组较D组增生明显.炎症因子hs-CRP,IL-6在B、C、D、A中的检测水平依次下降,B组较A组、B组较C组、B组较D组、C组较D组差异均有统计学意义（P＜0.05）.结论 普伐他汀有降低炎症因子,抑制动脉粥样硬化形成的作用.