氟伐他汀对兔动脉粥样硬化血管壁NF-κB和PDGF表达的影响

目的:观察氟伐他汀对动脉粥样硬化(AS)家兔模型血管壁核因子-kappaB(NF-κB)、血小板源性生长因子-A(PDGF-A)表达及血管平滑肌细胞(SMC)增殖的影响,以探讨氟伐他汀抗AS的作用机制。方法:雄性新西兰家兔32只,随机分为对照组、高脂饮食组、氟伐他汀组。喂养12周后处死动物并留取主动脉标本,观察组织形态学变化,用免疫组化法观察NF-κB、PDGF-A蛋白及SMC增殖细胞核抗原(PCNA)表达,用原位杂交法观察NF-κBmRNA表达,应用RT-PCR检测PDGF-AmRNA表达。结果:氟伐他汀组与高脂饮食组比较,AS病变明显减轻(P<0.01);PCNA表达由(29.8±3.0)%减弱为(13.5±4.5)%(P<0.01);PDGF-A表达由(73.9±6.2)%减弱为(46.9±4.2)%(P<0.01)。PDGF-AmRNA表达由(0.73±0.019)减弱为(0.50±0.028)(P<0.01)。NF-κB由(40.3±5.9)%减弱为(17.3±2.4)%(P<0.01);NF-κBmRNA表达由(41.7±5.5)%减弱为(19.6±1.7)%(P<0.01)。PDGF-A蛋白表达与PCNA表达呈正相关(P<0.05);NF-κB与PDGF-A蛋白表达呈正相关(P<0.05)。结论:氟伐他汀抗AS的形成,抑制SMC增殖,其作用机制可能与抑制NF-κB活性、下调PDGF-A表达有关。     

脂多糖诱导的血管外膜炎症对兔股动脉内膜增生的影响及机制

通过用脂多糖诱导兔股动脉外膜炎症,来观察其对内膜增生的影响,并用免疫组织化学法观察股动脉壁核因子κB p65的表达情况,从而探讨外膜炎症对内膜增生影响的分子机制。高脂饮食饲养新西兰大耳白兔24只,两侧股动脉按实验要求分为分为脂多糖组(n=24)和对照组(n=24)。制备用脂多糖诱导的外膜炎症模型,于术后0天(n=8)、3天(n=8)和2周(n=8)处死动物取得股动脉标本,HE染色观察形态学变化和内膜增生情况,同时用免疫组织化学方法镜下观察核因子κB p65在动脉壁的表达。结果发现3天和2周时,脂多糖组血管外膜和内膜面炎症细胞明显增多。在3天时,脂多糖组血管内皮细胞和外膜细胞在胞浆中出现核因子κB p65阳性表达。计算机图象分析发现,2周时脂多糖组内膜面积(0.93±0.14mm2)和对照组(0.75±0.15mm2)相比有明显差异(P<0.05)。结果提示脂多糖诱导的血管外膜炎症可导致兔股动脉内膜增生,而在内膜增生之前伴随着血管内皮细胞和外膜细胞核因子κBp65的阳性表达,外膜炎症可能是通过激活上述细胞中的核因子κB从而启动炎性细胞因子的转录导致内膜增生。     

氟伐他汀对抗磷脂综合征患者血清诱导的人血管内皮细胞MMP-9的影响

目的探讨氟伐他汀对抗磷脂综合征（APS）患者血清诱导的人血管内皮细胞基质金属蛋白酶-9（MMP-9）表达的影响及可能机制。方法体外培养人脐静脉内皮细胞（HUVEC）,分别用培养基、健康人血清、APS患者血清、APS患者血清加不同浓度氟伐他汀及APS患者血清加不同浓度氟伐他汀加甲羟戊酸处理。双抗体夹心酶联免疫吸附试验（ELISA）检测培养液中MMP-9浓度,RT-PCR检测MMP-9mRNA表达水平,Western-blot印迹法检测核因子-κBp65（NF-κBp65）蛋白表达水平。结果与对照组相比,APS患者血清可诱导MMP-9及NF-κBp65表达增加（P〈0.05）,而氟伐他汀对上述效应有剂量依赖性抑制作用（P〈0.05）,这种作用可以被甲羟戊酸阻断。结论氟伐他汀可能通过抑制NF-κB途径来抑制APS患者血清诱导的人血管内皮细胞MMP-9表达增加。     

血管黏附蛋白-1、核因子-κB在动脉粥样硬化斑块中的表达及其意义

目的探讨动脉粥样硬化(AS)血管中血管黏附蛋白-1(VAP-1)、核因子-κB(NF-κB)的表达水平,并分析两者的相互关系及其与AS发生发展的关系。方法应用免疫组化方法检测5例AS血管标本和1例正常血管标本中VAP-1、NF-κB的表达水平,分析VAP-1、NF-κB在二者表达中的相关性,并探讨其病理意义。结果VAP-1、NF-κB在AS血管中的阳性表达分别为(18.16±10.91)/HP和(27.12±9.56)/HP;NF-κB在正常血管仅有少量表达或呈未活化的状态,为(8.80±4.44)/HP,VAP-1在正常血管仅外膜轻度着色。VAP-1、NF-κB的表达之间呈明显正相关(r=0.558,P=0.004)。结论VAP-1、NF-κB的表达与AS发生发展密切相关,VAP-1在动脉粥样硬化斑块移行的平滑肌细胞中有大量表达。     

阿托伐他汀对心肌缺血再灌注老年大鼠NF-κBp65、COX-2表达的影响

目的 探讨阿托伐他汀对心肌缺血再灌注老年大鼠NF-κBp65、COX-2表达的影响.方法 健康Wistar老年大鼠30只,18月龄,随机分为3组,假手术组(S组)、缺血再灌注组(I/R组)、阿托伐他汀组(AT组),每组10只.采用结扎左冠状动脉前降支制备心肌缺血再灌注模型.观察阿托伐他汀对缺血再灌注老年大鼠血清中肌酸激酶同工酶(CK-MB)、天门冬氨基转移酶(AST)、乳酸脱氢酶(LDH)溢出量的影响;采用免疫组化法观察心肌缺血再灌注后心肌组织细胞中NF-κBp65及COX-2的蛋白表达.结果 与S组比较,I/R组心肌组织中CK-MB、AST及LDH含量明显增高,NF-κBp65的活性增高,COX-2的蛋白表达明显增加均有统计学意义(P ＜0.001);AT组中CK-MB、AST及LDH含量、NF-κBp65及COX-2略升高均有统计学意义(P＜0.01).结论 CK-MB、AST、LDH的含量及NF-kBp65和COX-2在心肌缺血再灌注中均有高水平表达,提示炎症参与了心肌缺血再灌注,机制可能是NF-κBp65通过对COX-2的转录调控发挥了重要作用;阿托伐他汀可抑制NF-κBp65活性,降低COX-2的蛋白表达水平,减轻I/R心肌炎症反应,对心肌起保护作用.     

胰岛素、血管紧张素Ⅱ对人血管内皮细胞NF-κB的激活和血脂康干预的影响

目的观察胰岛素、血管紧张素Ⅱ(Ang Ⅱ)对体外培养的人脐静脉内皮细胞(Human umbilical vein endothelialcells,HUVECs)NF-κB的激活及血脂康干预后的影响。方法体外培养人脐静脉内皮细胞株(ECV-304),2~3代用于实验。细胞用0.5%胎牛血清培养液培养24小时后分成七组;正常对照组、胰岛素组(100uI/ml)、Ang Ⅱ组(5×10-8mol/ml)、胰岛素+Ang Ⅱ组、胰岛素+血脂康组(150ug/ml)、Ang Ⅱ+血脂康组、胰岛素+Ang Ⅱ+血脂康组。加血脂康的各组,血脂康预先孵育2h,再加胰岛素或/和Ang Ⅱ共同孵育。在4h时间点上,分别用免疫细胞化学方法测各组内皮细胞NF-κBp65的核易位阳性率,用免疫荧光和流式细胞仪检测其活性。结果①胰岛素、Ang Ⅱ、胰岛素+Ang Ⅱ刺激4h后,内皮细胞NF-κBp65的核易位阳性率(%)分别为95.5±3、96.6±3、96.4±4,显著高于对照组(4.5±2)(P<0.05),血脂康几乎完全抑制胰岛素、Ang Ⅱ、胰岛素+Ang Ⅱ所致的NF-κBp65核易位阳性率的增加(7.3±3、6.9±46、.3±2)(P<0.05)。②胰岛素、Ang Ⅱ、胰岛素+Ang Ⅱ刺激4h后,内皮细胞NF-κB活性分别为6.55±0.53、7.23±0.36、10.29±0.69,显著高于对照组(3.26±0.37)(P<0.05);与单用胰岛素或Ang Ⅱ比,胰岛素+Ang II使NF-κB活性增加更明显(P<0.05);血脂康能明显抑制NF-κB的活性(4.44±0.49、3.98±0.24、5.02±0.39)(P<0.05)。结论胰岛素、Ang Ⅱ均能激活内皮细胞NF-κB,促进NF-κBp65的核易位,有致动脉粥样硬化(AS)作用。血脂康能抑制内皮细胞NF-κB的激活,具有调脂外的抗AS作用。     

阿托伐他汀对糖尿病大鼠视网膜核因子-κB表达的影响

目的 探讨他汀类药物对糖尿病大鼠视网膜核因子(NF)-κB表达的影响及其可能机制.方法 雄性SD大鼠60只,随机抽40只腹腔注射链脲佐菌素65 mg/kg建立糖尿病模型,余20只为正常对照组.成模大鼠随机分成两组,糖尿病非药物干预组及阿托伐他汀干预组.干预组予阿托伐他汀(2 mg·kg-1·d-1)灌胃,对照组及糖尿病非药物干预组给予等量饮用水.大鼠分别于3,6个月时按比例处死.取一眼视网膜组织抽提RNA,另一眼固定后做免疫组织化学观察.RT-PCR法扩增NF-κB基因,比较3组大鼠的NF-κB mRNA表达差异.免疫组织化学法观察NF-κB蛋白表达差异.结果 PCR结果示糖尿病大鼠视网膜NF-κB mRNA表达较正常大鼠明显增高(P＜0.05),药物干预的大鼠,NF-κB mRNA表达比糖尿病非药物干预组明显减少(P＜0.05).免疫组织化学结果示视网膜上,NF-κB主要分布在血管层,糖尿病大鼠视网膜中NF-κB阳性的细胞比正常组明显增多(P＜0.05),且着色较深.阿托伐他汀干预组NF-κB阳性的细胞比糖尿病大鼠明显减少(P＜0.05),且着色较浅.结论 阿托伐他汀能降低糖尿病大鼠视网膜中NF-κB mRNA及NF-κB蛋白质的表达,减缓视网膜病变进展.     

高血压大鼠心脏钙调蛋白磷酸酶与核因子κBp65的表达

目的探讨钙调蛋白磷酸酶(caicineurin)、核因子κBp65(NFκBp65)在高血压心血管重构信号转导通路的作用。方法建立腹主动脉缩窄高血压大鼠模型,以尾动脉测压法观察大鼠血压变化,用免疫组织化学和形态计量学方法,观察calcineurin、NFκBp65在心脏原位蛋白表达和心脏重量及其系数的变化。结果与假手术组比较,高血压大鼠血压明显升高[(144.70±4.85)vs(110.00±4.00)mmHg,P<0.01;(151.40±14.86)vs(114.36±5.5)mmHg,P<0.01]、心脏重量及其系数显著增加[(1.87±0.07)vs(1.51±0.13)g,P<0.01,(0.43±0.02)vs(0.33±0.01)g/100g,P<0.01]、心脏重构,钙调蛋白磷酸酶与NFκBp65在心脏过表达,而且阳性表达面积和阳性表达面积百分比增大[(107380.36±9268.64)vs.(14537.64±12169.42)μm2,P<0.01;(54797.00±17483.46)vs(3501.43±2919.18)μm2,P<0.01]。结论calcineurin与NFκBp65过表达参与了腹主动脉缩窄性高血压心血管重构的发生。     

高脂血症兔主动脉NF-κB、VCAM-1和VEGF的表达及氟伐他汀的影响

目的观察高脂饮食后兔主动脉NF-κB、VCAM－1、VEGF的表达及氟伐他汀的影响，探讨高脂血症引起动脉粥样硬化可能的分子生物学机制和氟伐他汀的作用。方法健康雄性新西兰大耳白兔30只，随机分为5组，高脂饮食4周、6周、8周组，正常饮食和高脂饮食加氟伐他汀组。到规定时间点，处死动物取主动脉标本，观察组织形态学变化，用免疫组化的方法检查NF-κB、VCAM－1和VEGF的表达。结果①高脂血症可以引起NF-κB、VCAM－1、VEGF增加，与对照组比较差异有统计学意义（P〈0．01）。②LDL水平与NF-κB表达呈显著正相关（r=0．922，P〈0．01）；NF-κB与VCAM－1、VEGF呈显著正相关（r＝0．937，P〈0．01，r=0．894，P〈0．01）。③氟伐他汀可以减少NF-κB、VCAM－1和VEGF的表达（P＜0．05）。结论NF-κB、VCAM－1和VEGF参与了动脉粥样硬化的进程，炎症是高脂血症的伴随因素，引起了细胞增殖，与动脉粥样硬化密切相关：氟伐他汀可以减少其表达起到抗动脉粥样硬化作用。     

拜阿司匹林对小鼠主动脉核转录因子-κB与基质金属蛋白酶-9表达的调控

目的：观察拜阿司匹林对小鼠主动脉核转录因子-κB（NF--κB）与基质金属蛋白酶-9（MMP-9）表达的调控作用。方法：40只13周龄小鼠分为拜阿司匹林组（给高脂饲料。拜阿司匹林6mg／kg灌胃），氟伐他汀组（给高脂饲料，氟伐他汀3mg／kg灌胃），模型组（给高脂饲料，生理盐水1ml灌胃），正常对照组（给予普通饲料·生理盐水1ml灌胃），每组10只，17周后，取主动脉，以免疫组化法观察其NF—κB和MMP-9表达的程度。结果：较之对照组模型组，小鼠主动脉粥样斑块的NF--κB与MMP-9表达明显增加，拜阿司匹林组和氟伐他汀组均显著降低其表达（P均〈0.01），拜阿司匹林组和氟伐他汀组间其表达水平无显著差异（P〉0.05）。结论：拜阿司匹林可以降低NF-κB与MMP-9的表达．从而抑制血管内炎症反应和基质纤维蛋白的降解，起到治疗动脉粥样硬化的作用。     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

Pulmonary sporotrichosis in Oklahoma in susceptibilities in vitro

Six cases of pulmonary sporotichosis were observed in 2 institutions in Oklahoma City, Okla. Three of the patients were treated with iodides with or without surgery. Although one patient required a second course of iodides, the patients have remained well after at least 34 months of follow-up. Three patients treated with amphotericin B, single course as well as multiple courses, and other antifungal agents (hydroxystilbamidine and miconazole) have all relapsed. These cases and a reviewed of more than 40 cases of pulmonary sporotrichosis susceptibilities of Sporothrix schenckii that we observed in vitro suggest that amphotericin B is not an effective agent for the treatment of pulmonary sporotrichosis. It is our opinion that the treatment of choice for pulmonary sporotrichosis is a supersaturated solution of potassium iodide. If the patient is allergic to the medication or fails to respond, then a combination of amphotericin B plus flucytosine may be tried.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

Differences in outcome in primary angioplasty in women.

BACKGROUND: In acute myocardial infarction (AMI), primary percutaneous transluminal coronary angioplasty (PTCA) has proved to be the best therapeutic approach. Several factors have been associated with worse outcome in AMI in females. Are there differences in outcome in women undergoing PTCA for AMI? AIM: To evaluate gender influence on clinical outcome and in-hospital mortality in patients with AMI who undergo primary percutaneous interventions. METHODS: We studied 245 consecutive patients (72 women, 29.4 %), who underwent primary PTCA between January 2000 and December 2001. The following parameters were analyzed: risk factors for coronary artery disease including hypertension, diabetes, smoking, hypercholesterolemia and family history, previous AMI, PTCA or angina, pain-to-balloon time, extent of coronary disease and outcome. RESULTS: Female patients were older (67.9+/-11.6 vs. 59.6+/-13; p < 0.001) with a higher prevalence of hypertension (65.3 % vs. 47.4 %; p < 0.05) and angina (29.0 % vs. 16.0 %; p < 0.05) and lower prevalence of smoking (27.8 % vs. 54.3 %; p < 0.001). Pain-to-balloon time was longer in women (6.8+/-4.1 vs. 5.4+/-3.7 hours; p < 0.05). Extent of coronary disease was similar in both groups. Glycoprotein IIb/IIIa inhibitors were used in 84.7 % of women and 90.8 % of men. The frequency of hemorrhagic complications (5.6 % vs. 5.2 %) and arrhythmias (15.3 % vs. 10.4%) and in-hospital mortality (9.7 6.4 %) were higher in females, although without statistical significance (p = NS). Hospitalization time was similar in both groups. CONCLUSIONS: Despite the growing awareness of a gender bias in therapeutic approaches to AMI, there are still some differences in outcome, with a trend towards higher mortality rates in women. Older age and longer pain-to-balloon time could account for this.