长期暴露于空气污染与女性心血管事件发生率之间的关系

大气细颗粒物污染与心血管疾病相关，但以往的研究只评估了死亡率和城市之间暴露量的差别。本试验观察了长期暴露于空气动力学粒径小于2．5ixm（PMz5）的颗粒物与心血管事件之间的联系。方法：1994—1998年，纳入美国36个都市地区65893例既往无心血管疾病的绝经后女性，中位随访期为6年。利用距离每例女性住处最近的监测仪评估其暴露于空气污染的水平。校正年龄、民族／种族、吸烟状况、受教育程度、家庭收入、体重指数、有无糖尿病、高血压或高脂血症等因素后，评价其首次心血管事件发生的风险比。     

实验性糖尿病合并动脉粥样硬化大鼠模型的建立

目的:建立2型糖尿病合并动脉粥样硬化的大鼠模型。方法:选取48只成年雄性SD大鼠,其中38只制成T2DM模型,分成HD组(SD大鼠10只)、STZ组(T2DM大鼠15只)和STZ+HD组(T2DM大鼠23只),HD组和STZ+HD组喂以高脂饲料,STZ组喂以基础饲料,观察血糖、胰岛素、血脂水平和胰腺和胸主动脉病理变化。结果:第1、3、6个月末,STZ、STZ+HD组的FBG、BPG、胰岛素、血脂均明显高于HD组,差异有统计学意义(P<0.05),第3、6个月末,STZ+HD组的BPG、血脂明显高于STZ组,6个月STZ+HD组胰岛素水平较STZ组高,差异有统计学意义(P<0.05)。胰腺和主动脉病理学观察有显著改变。结论:腹腔注射STZ+高脂喂养可成功复制糖尿病合并动脉粥样硬化大鼠模型。     

野马追提取液对动脉粥样硬化家兔炎症反应的防治作用

目的 观察野马追提取液(lindley eupatorium herb,LEH)对动脉粥样硬化(atherosclerosis,AS)家兔模型血管壁炎症的影响.方法 将36只家兔完全随机分为6组:正常对照组,模型组,阳性药物组及野马追大、中、小剂量组,分别给予基础饲料,高脂饲料及高脂饲料分别添加辛伐他汀2.2 mg/kg,野马追8.34、4.17、2.08 g/kg处理.分别于6、10周检测血浆中脂质及炎性标志物C反应蛋白( C-reactive protein,CPR)、血管内皮舒张因子一氧化氮(NO)的水平,病变组织中血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)mRNA的表达;测量粥样斑块的面积及厚度.结果 模型组血脂水平及主动脉粥样硬化斑块面积与正常组比较有明显升高[第10周TC:( 1.39±0.23) mmol/L vs (46.30±6.73)mmol/L,P＜0.05;脂质斑块面积占主动脉面积比:0％ vs (89.61±7.85)％,P＜0.05];野马追各组血浆中CPR及组织中VCAM-1 mRNA的表达均明显降低[(5.15±1.42)、(5.69±1.45)、(6.36±1.43)mg/L vs (8.34±1.85) mg/L,P＜0.05],NO含量明显升高[(117.41±9.61)、(87.87±13.47)、(64.34±11.18) μmol/L vs(47.29±8.29)μmol/L,P＜0.05].结论野马追对动脉粥样硬化有良好的防治作用,其机制可能与抗炎相关.     

短期雾霾刺激对健康成年人鼻腔炎性反应状态的影响

目的观察短期重度雾霾对健康成年受试者鼻部症状、功能和炎性反应状态的影响。方法 23例居住于北京市中心的健康成年志愿者参与本项研究。分别于一次持续5 d的雾霾前后记录受试者的鼻部不适症状、检查其鼻功能、口鼻呼出一氧化氮(nitric oxide,NO)浓度,并收集鼻分泌物用于细胞因子浓度测定。结果在雾霾发生后的第二次访视中,受试者反映有不同程度的鼻部不适感,包括鼻堵、鼻痒、鼻干和鼻后滴漏等。鼻功能检查示鼻阻力由雾霾前的(0.18±0.01)Pa/(cm3·s)升高至雾霾后的(0.24±0.02)Pa/(cm3·s)(P=0.001);鼻腔容积由雾霾前的(15.06±052)cm3下降至雾霾后的(7.79±0.74)cm3(P=0.000);鼻腔最小截面积由雾霾前的(1.20±0.05)cm~2下降至雾霾后的(1.06±0.04)cm~2,差异有统计学意义(P=0.006)。与雾霾发生前相比较,经鼻或经口呼出NO浓度均在雾霾发生后明显升高。雾霾后,鼻分泌物中的Th2型细胞因子eotaxin和白细胞介素-5(interleukin-5,IL-5)、趋化因子C-C-基元配体7[chemokine(C-C motif)ligand 7,CCL7]、以及促炎性反应因子IL-8浓度显著升高,而Th1型细胞因子干扰素(interferon-γ,IFN-γ)以及免疫调节因子IL-10和转化生长因子-β(transforming growth factor-β,TGF-β)浓度显著下降。结论短期雾霾刺激可使健康成年人的鼻腔分泌物炎性反应介质倾向于Th2型分化,而参与免疫调节、抑制细胞增生、促进细胞外基质形成和损伤修复的细胞因子表达下降。鼻黏膜局部炎性反应状态的失衡一方面可直接使鼻腔有效通气面积减少,引发鼻部症状,另一方面可使个体易受过敏原、病原体或其他理化刺激的影响,这也是未来的研究方向。     

血管性痴呆动物模型研究概况

血管性痴呆是由于血管源性的脑部病灶所导致的严重认知功能障碍,它不是一种单一的疾病,而是由于多种发病原因引起的多类型综合征,皮质下小动脉病变、多发梗塞、脑慢性低灌注以及脑血管淀粉样改变等都是引起血管性痴呆的不同病因。针对不同的病因制备血管性痴呆动物模型是研究血管性痴呆发病机制、治疗药物等的重要条件．本文就近几年来血管性痴呆动物模型的制备做以综述。     

北京市大气污染对成人呼吸系统症状发生的长期影响

目的:研究长期生活在不同污染程度地区的成人呼吸系统症状发生率之间的差异,以便为将来开展更为深入、广泛的调查研究提供基础数据。方法:于2008年10月,在北京市选取污染程度相对严重的某城区和相对洁净的某郊区为研究地点,采用整群抽样的方法,分别选择4所和3所小学的学生家长为研究对象(共计9 052名成人),使用国际标准化问卷对成人呼吸系统症状的发生情况进行调查。通过环境状况公报、环境保护局和统计年鉴等了解研究该地区近5年的大气污染物浓度数据。采用卡方检验分析城、郊区成人(居住时间2年及以上)呼吸系统症状发生率和年龄标准化发生率之间的差异。结果:与郊区相比,城区成人的持续性咳痰(3.06%vs.2.43%,P<0.05)和哮喘样症状(0.65%vs.0.31%,P<0.01)的年龄标准化发生率相对较高,而气短的年龄标准化发生率则相对较低(0.75%vs.1.12%,P<0.05),其他呼吸系统症状的发生率在两区之间的差异不具有统计学意义。结论:本研究提示大气污染物对成人呼吸系统症状的发生存在一定的长期效应,其具体作用特征有待进一步研究。     

小鼠皮下气囊慢性炎症模型的建立

目的:探索建立小鼠皮下慢性炎症模型的方法.方法:在小鼠皮下制作气囊,然后向气囊内注入不同致炎物(脂多糖和卡介苗),建立两种慢性炎症模型,观察皮下慢性炎症发生、发展情况及慢性炎症生成率.对照组小鼠气囊内注入生理盐水.结果:实验组小鼠皮下气囊壁慢性炎症生成率均为100％,对照组小鼠气囊壁无慢性炎症反应发生.使用t检验对各组小鼠皮下气囊壁的重量进行统计分析.脂多糖组与对照组相比,在造模后第5、7、12、14和16天时差异有统计学意义(P＜0.05)；卡介苗组与对照组相比在第5天时差异无统计学意义(P＞0.05),在造模后第7、12、14和16天时差异有统计学意义(P＜0.05).脂多糖和卡介苗组的气囊壁均在造模后第7天出现典型的慢性炎症表现.脂多糖和卡介苗组气囊灌洗液的中性粒细胞在造模5d逐渐为淋巴细胞和单核巨噬细胞取代,对照组灌洗液未检出炎细胞.结论:在小鼠皮下制作气囊,注入脂多糖或卡介苗可以成功地建立小鼠皮下气囊慢性炎症模型.此模型能较好地模拟在单一致炎因子存在情况下引起的慢性炎症状态.     

Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution

Context  Associations have been found between day-to-day particulate air pollution and increased risk of various adverse health outcomes, including cardiopulmonary mortality. However, studies of health effects of long-term particulate air pollution have been less conclusive. Objective  To assess the relationship between long-term exposure to fine particulate air pollution and all-cause, lung cancer, and cardiopulmonary mortality. Design, Setting, and Participants  Vital status and cause of death data were collected by the American Cancer Society as part of the Cancer Prevention II study, an ongoing prospective mortality study, which enrolled approximately 1.2 million adults in 1982. Participants completed a questionnaire detailing individual risk factor data (age, sex, race, weight, height, smoking history, education, marital status, diet, alcohol consumption, and occupational exposures). The risk factor data for approximately 500 000 adults were linked with air pollution data for metropolitan areas throughout the United States and combined with vital status and cause of death data through December 31, 1998. Main Outcome Measure  All-cause, lung cancer, and cardiopulmonary mortality. Results  Fine particulate and sulfur oxide–related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality. Each 10-µg/m³ elevation in fine particulate air pollution was associated with approximately a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer mortality, respectively. Measures of coarse particle fraction and total suspended particles were not consistently associated with mortality. Conclusion  Long-term exposure to combustion-related fine particulate air pollution is an important environmental risk factor for cardiopulmonary and lung cancer mortality.      

家兔绝经后动脉粥样硬化模型的建立及补肾治疗对其的影响

目的　建立家兔绝经后动脉粥样硬化模型并探讨补肾治疗对其的影响。方法　新西兰家兔分别用去势 ,高脂饲料+免疫损伤 ,去势 +高脂饲料 +免疫损伤三种方法造模 ,12周后检测相关指标。结果　去势 +高脂饲料 +免疫损伤组模型动物改变最明显 ,雌激素水平下降 ,血清胆固醇、三酰甘油等明显升高 (P <0 .0 5) ,并伴血管壁的损害 ;补肾中药能缓解上述改变。结论　新西兰家兔经去势 +高脂饲料 +免疫损伤处理可造成绝经后动脉粥样硬化模型 ,其改变可能与肾虚有一定联系     

心理应激性内皮损伤动物模型的初步研究

目的 采用愤怒心理应激建立血管内皮损伤动物模型,并探讨血管内皮损伤的情况.方法 雄性SD大鼠随机分为对照组、模型组,采用愤怒心理应激建立血管内皮损伤模型,放射免疫法检测血浆皮质醇的含量,采用ELISA法检测血浆肾上腺素、血管性血友病因子(vWF),硝酸还原酶法检测血浆NO含量,HE染色及扫描电镜观察血管内皮结构的损伤情况.结果 模型组血浆皮质醇、肾上腺素、vWF水平明显高于对照组(P<0.05),血浆NO含量明显低于对照组(P<0.05),扫描电镜观察血管内皮细胞明显受损.结论 该模型是较理想的心理应激内皮损伤模型.     

炎症与动脉粥样硬化研究现状

动脉粥样硬化性心血管疾病是当今危害人类健康的首位疾病 ,其发病机制尚不完全清楚 ,最近研究认为动脉粥样硬化(atherosclerosis ,AS)的发生是多因素综合作用的结果。其中 ,炎症反应在AS的发生、发展及其急性并发症形成过程中有着重要作用。本文就近年有关炎症与AS关系的研究进展作一综述。1　炎症反应与AS1 1　炎症反应在AS形成中的细胞学基础　在许多AS的动物模型中 ,动脉壁内炎症征象与初期的脂质沉积同时发生。进一步研究将注意力集中在产生这种现象的机制上。正常的血管内皮细胞是不会粘附白细胞的 ,但给动物以致AS饮食后不久 ,…     

基于慢性缺血应激建立血管性抑郁症动物模型

目的 旨在建立血管性抑郁症(vascular depression, VD)的理想动物模型。方法 选用SD大鼠40只,采用数字表法随机分为4组:1手术组:双侧颈总动脉结扎(ligation of bilateral common carotid arteries, LBCCA);2假手术组:同手术组处理,但不结扎;3抑郁组:慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)结合孤养,不进行手术;4模型组:LBCCA叠加CUMS,结合孤养。连续观察21 d,观测大鼠体质量变化、行为学改变、脑血流量变化以及大鼠大脑基质金属蛋白酶(matrix metalloproteinases, MMPs)、脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)、酪氨酸激酶受体B(tropomyosin related kinase B, TrkB)蛋白及其mRNA表达水平的变化。结果 与假手术组比较,模型组和抑郁组大鼠体质量、糖水消耗百分率、旷场试验运动距离及站立次数均明显降低(P<0.05或P<0.01),手术组及模型组大鼠脑血流量明显降低(P<0.01),手术组及模型组MMP-2及MMP-2 mRNA表达水平显著增高(P<0.01),抑郁组及模型组海马内BDNF/TrkB及BDNF/TrkB mRNA表达均明显降低(P<0.01或P<0.05)。结论 LBCCA叠加CUMS结合孤养方法较好地模拟了抑郁核心症状快感缺乏、运动和探索能下降的行为特征和神经血管单元(neurovascular unit, NVU)稳态失衡的病理机制,是较为理想的血管性抑郁模型,可用于药理实验及治疗效果机制研究。     

芪苈强心胶囊联合大剂量阿托伐他汀对高血压合并动脉粥样硬化患者炎症和血管微循环的影响

目的 探讨芪苈强心胶囊联合大剂量阿托伐他汀对高血压合并动脉粥样硬化患者炎症反应及血管微循环的影响。 方法 选取2015年1月—2018年12月间中国人民解放军第七十二集团军医院收治的192例高血压合并动脉粥样硬化患者,采用随机数字法将患者均分为2组,每组96例。对照组给予阿托伐他汀治疗,联合组在此基础上加用芪苈强心胶囊治疗。治疗后,比较2组炎症反应(hs-CRP、TNF-α、IL-6)、血脂(TG、TC、HDL-C、LDL-C)、血压(SBP、DPB)、血流变(Nbh、Nbl、Np、Fh)、内皮功能(NO、H₂S、ICAM-1)及斑块情况(IMT值、PV)的变化。 结果 治疗后,2组炎症反应、血脂(TG、TC、LDL-C)、血压、血流变均明显降低(均P<0.05),且联合组均显著低于对照组(均P<0.05)。治疗后,2组HDL-C、NO、H₂S水平显著提高(均P<0.05),且联合组明显高于对照组(均P<0.05);2组ICAM-1水平显著降低,且联合组明显低于对照组(均P<0.05)。治疗后,对照组IMT、PV水平无明显变化(均P>0.05);联合组IMT、PV水平显著降低(均P<0.05)。治疗后联合组的总有效率(88.5%)显著高于对照组(70.8%),χ2=9.299,P=0.002。 结论 相比于单用阿托伐他汀,芪苈强心胶囊联合大剂量阿托伐他汀可更为有效地减轻高血压合并动脉粥样硬化患者炎症反应,调节患者血管微循环,治疗效果较显著。      

Relative nephrotoxicity of cephalosporin antibiotics in an animal model

An animal model is described in which mild transitory renal impairment is induced with glycerol and the nephrotoxic effects of cephalosporin antibiotics and furosemide studied. Cephaloridine and cephalothin were found to produce extensive acute tubular necrosis in rats when given in subnephrotoxic doses in combination with furosemide; this damage occurred at serum antibiotic levels not much higher than those obtained in clinical practice. No significant renal damage was found with cephalexin or Cephapirin given in equivalent dosage. It is suggested that the cephalosporin antibiotics should be used with caution in the presence of even minor transient renal impairment and particularly if furosemide is being given concurrently.     

心肌梗死的动物模型制作

心肌梗死是严重危害人类健康的心血管疾病，也是主要致死因素之一。在心血管疾病研究中，动物模型被广泛用于发病机制和药物治疗研究。研究目的不同则所需的动物模型平台亦不同，心肌梗死动物模型的有效建立是完成相关实验的前提，对研究急、慢性心肌梗死的病理演变过程、诊断及治疗均有重要意义。     

炎症诱导的新型大鼠动脉粥样硬化模型的建立及Rb1的防治作用

目的 通过激发大鼠炎症反应建立新型动脉粥样硬化(AS)动物模型并观察人参皂苷Rb1的抗AS作用.方法 模型组采用酵母多糖混悬液(20 mg/kg)每隔3d腹腔注射一次,引发大鼠持续性炎症;相同方法注射无菌石蜡液作为对照组;Rb1组同时腹腔注射Rb1(40 mg/kg);所有大鼠均喂食高脂饲料,实验共10周.分别通过苏丹染色、透射电镜、real time PCR、免疫组化、ELISA观察大鼠主动脉壁大体标本、超微结构、NFκB、TNFα、IL6的表达.结果 模型组可见红染的脂纹、斑块形成,电镜显示内膜下层出现吞噬脂滴的泡沫细胞,NFκB/P65高表达于主动脉壁的内膜层,TNFα、IL6水平均明显高于对照组,经Rb1干预后大体标本可见AS病变明显减轻,电镜下未见泡沫细胞,NFκB、TNFα、IL6水平均较模型组显著降低.结论 在高脂喂饲的基础上持续炎症刺激能够成功诱导大鼠AS模型,人参皂苷Rb1能够通过抑制炎症反应抗AS.     

Establishment of an animal model with hypoxic hepatitis

Objective To establish and evaluate an animal model with hypoxic hepatitis.Methods 100 male Sprague-Dawley rats were randomised into two groups.70 rats received isoproterenol(5mg /kg /day)intraperitoneally and the remaining 30 were used as control and received placebo(0.05% ascorbic acid in 0.9% NaCl)on a daily basis for 7 days.Liver function tests were carried out to demonstrate the establishment of hypoxic hepatitis.Brain-natriuretic pep-tide(BNP)was investigated to diagnose heart failure.Histopathological examination of the heart and liver were performed.Results Overall mortality rate following 7 days of isoproterenol injection was 5%.Raised BNP level(130 + 6 pg /ml)confirmed the development of heart failure while after 14 days the abnormally raised liver function tests(ALT:840 + 4U /L,AST:1818 + 2U /L,ALK.Phos:484 + 4U /L,LDH:922 + 2U /L)indicated the establishment of HH.Histopathological exams revealed that the atria and ventricles were significantly hypertrophied and fibrosis was observed in the ventricles.The specimen of the liver showed centrilobular necrosis and apoptosis of the hepatocytes.Conclusion These results suggest that inducing heart failure in rats is a favorable approach and is technically feasible in terms of establishment of hypoxic hepatitis in an animal model.     

Establishing an animal model of unstable atherosclerotic plaques

Background Atherosclerotic plaque rupture and coronary thrombosis are the main causes of acute coronary syndromes. However, there is no animal model of unstable atherosclerotic plaques. The presence of the p53 gene in advanced atherosclerotic plaques and the sensitivity to p53-induced apoptosis of smooth muscle cells isolated from these plaques prompted us to build an animal model of unstable atherosclerotic plaques using p53 gene transfer. Methods Sixty-four New Zealand white rabbits were randomly divided into two groups: group A (n=54) and group B (n=10). Rabbits in group A underwent balloon-induced abdominal aortic wall injury and were then given a diet of 1% cholesterol, while rabbits in group B were given a diet of 1% cholesterol without the induction of aortic wall injury. At the end of the eighth week, rabbits in group A were randomly divided into two subgroups: group A1 (n=27) and group A2 (n=27). Recombinant adenovirus carrying p53 or β-galactosidase (LacZ) genes were injected through a catheter into the aortic segments rich in plaques in groups A1 and A2, respectively. Two weeks later, 10 rabbits each from groups A1 and A2 were killed to observe the occurrence of spontaneous plaque ruptures, and the remaining rabbits in groups A1, A2, and B all underwent pharmacological triggering with an injection of Chinese Russell’s viper venom (CRVV) and histamine. Results The over expression of p53 in group A1 ［(32.4±10.2)% vs (15.8±3.6)% in group A2 and (16.2±6.7)% in group B, P&lt;0.001, respectively］ resulted in a marked increase in cellular apoptosis ［(2.5±0.8)% vs (1.0±0.3)% in group A2 and (0.9±0.4)% in group B, P&lt;0.01, respectively］, an accumulation of inflammatory cells within the plaques, and a significant decrease in vascular smooth muscle cells (VSMCs) and in the thickness of the fibrous caps. Although spontaneous plaque rupture was rare in group A1, plaque ruptures and thrombosis occurred in 12 rabbits with a total of 20 lesions after pharmacological triggering. By contrast, pharmacological triggering led to plaque rupture and thrombosis in only 5 rabbits for a total of 7 lesions in group A2 and in none of the rabbits in group B. Conclusion After transfection with human wild-type p53 gene and pharmacological triggering, plaque rupture and thrombosis occur in most atherosclerotic lesions in rabbits, thus offering a reliable model for the further study of unstable atherosclerotic plaques.