巨噬细胞集落刺激因子对小鼠腹腔巨噬细胞清道夫受体途径和细胞内胆固醇酯积聚的影响

为探索巨噬细胞集落刺激因子、清道夫受体、氧化型低密度脂蛋白与动脉粥样硬化的关系，观察了重组人巨噬细胞集落刺激因子对小鼠腹腔巨噬细胞清道夫受体途径的影响以及重组人巨噬细胞集落刺激因子对氧化型低密度脂蛋白所致细胞内胆固醇酯积聚的影响．结果发现重组人巨噬细胞集落刺激因子能增加培养的小鼠腹腔巨噬细胞表面的清道夫受体数目，使之对氧化型低密度脂蛋白的结合和降解呈现剂量和时间依赖性增加，并使细胞内胆固醇酯积聚增多．表明巨噬细胞集落刺激因子可通过增加清道夫受体数目使小鼠腹腔巨噬细胞对氧化型低密度脂蛋白的结合和降解增多，从而增加细胞内胆固醇酯含量，促进动脉壁内泡沫细胞形成．     

CD36与动脉粥样硬化

CD36是在多种组织细胞上表达的跨膜糖蛋白,属于B族清道夫受体.单核巨噬细胞上的CD36是吞噬摄取氧化型低密度脂蛋白的主要受体.除介导泡沫细胞形成外,CD36还有促进凝血和单核细胞聚集,促进炎症反应和氧化、凋亡等多种功能,其表达可被高度调控,是巨噬细胞泡沫化和动脉粥样硬化发生发展的重要因素.     

巨噬细胞内脂质代谢及泡沫细胞形成机制的研究进展

动脉粥样硬化是以动脉内膜下胆固醇积聚为特征的慢性疾病。泡沫细胞是构成动脉粥样斑块的主要成分,大多由于巨噬细胞内脂质代谢紊乱引起。巨噬细胞通过胞饮、清道夫受体介导的方式吞噬胞外胆固醇,在胆固醇酰基转移酶1(ACAT1)和中性胆固醇酯水解酶(nCEH)作用下维持细胞内脂质平衡,多余的胆固醇可以通过ATP结合盒转运体A1(ABCA1)、ATP结合盒转运体G1(ABCG1)和清道夫受体B1(SR-B1)排出。该文介绍巨噬细胞内胆固醇摄取、酯化水解和外溢过程,以及泡沫细胞形成的机制。     

细胞胆固醇流出通路研究进展

动脉粥样硬化的形成是动脉壁内泡沫细胞逐渐沉积的慢性炎症过程。循环中的氧化脂质特别是氧化型低密度脂蛋白胆固醇,以及一些体液因子、细胞因子均可引起单核巨噬细胞表面的清道夫受体表达增加,单核巨噬细胞吞噬大量含胆固醇的脂质,胆固醇流出减少,形成泡沫细胞,并在内皮下聚集,从而促进动脉粥样硬化的发生。     

阻断清道夫受体AⅠ对巨噬细胞源泡沫细胞基质金属蛋白酶及其组织抑制剂表达的影响

为探讨巨噬细胞源泡沫细胞基质金属蛋白酶及其组织抑制剂的表达及活性与清道夫受体AⅠ的关系，应用油红O染色、高效液相色谱法检测巨噬细胞的泡沫化，逆转录聚合酶链反应检测细胞清道夫受体AⅠ的表达，Westem blot明胶酶谱法观测巨噬细胞泡沫化后阻断清道夫受体AⅠ对THP—1细胞基质金属蛋白酶2、基质金属蛋白酶9、组织型基质金属蛋白酶抑制剂1及组织型基质金属蛋白酶抑制剂2表达的影呐。结果发现，THP—1细胞在佛波酯处理24h后有清道夫受体AⅠ的表达，清道夫受体AⅠ反义寡核苷酸及其抗体能显著降低基质金属蛋白酶2和基质金属蛋白酶9的蛋白表达和活性，并增加组织型基质金属蛋白酶抑制剂1和组织型基质金属蛋白酶抑制剂2的表达。结果提示，阻断清道夫受体AⅠ有助于基质金属蛋白酶与组织型基质金属蛋白酶抑制剂的平衡维持，从而抑制细胞外基质的降解。     

硫酸乙酰肝素蛋白聚糖及肝素对巨噬细胞脂质蓄积的抑制作用

用苏丹Ⅳ染色观察巨噬细胞内脂质聚积的变化；通过酶－荧光法检测巨噬细胞内胆固醇含量并检测125Ⅰ标记氧化型低密度脂蛋白降解量来反映巨噬细胞清道夫受体的活性，以探讨硫酸乙酸肝素蛋白聚糖及肝素对巨噬细胞脂质蓄积的影响及机制。结果发现，氧化型低密度脂蛋白（100mg／L）组巨噬细胞的胞浆内可见较多苏丹Ⅳ着色红染颗粒，氧化型低密度脂蛋白（100mg／L）十硫酸乙酰肝素蛋白聚糖（15．5mg／L）组0及氧化型低密度脂蛋白（100mg／L）十肝素（200mg／L）组巨噬细胞内红色颗粒明显少于氧化型低密度脂蛋白组；氧化型低密度脂蛋白十硫酸乙酰肝素蛋白聚糖组及氧化型低密度脂蛋白十肝素组巨噬细胞内总胆固醇和胆固醇酯的含量明显低于氧化型低密度脂蛋白组（P＜0．05，P＜0．01）；硫酸乙酰肝素蛋白聚糖组及肝素组125Ⅰ标记的氧化型低密度脂蛋白降解量均低于对照组。结果提示，硫酸乙酰肝素蛋白聚糖和肝素可能是通过下调清道夫受体活性减少了巨噬细胞对氧化型低密度脂蛋白的摄取而抑制脂质在巨噬细胞内的聚集和泡沫细胞的形成。     

巨噬细胞内吞脂质的分子机制

动脉粥样硬化性心脑血管疾病是危害人类健康最主要的杀手之一。一般认为，动脉粥样硬化（As）是一种巨噬细胞和淋巴细胞对侵入动脉壁的病原性脂蛋白所产生的炎症反应，最早肉眼可见的病变是脂纹的形成，其主要成分是大量摄取脂质后从巨噬细胞所衍变成的泡沫细胞。研究认为，脂质在巨噬细胞中的大量积聚主要由清道夫受体介导。在众多的清道夫受体中，A类清道夫受体是目前公认的介导氧化型低密度脂蛋白进入细胞的主要受体之一。     

羧甲基赖氨酸对RAW264.7源性泡沫细胞迁移的影响

目的探讨糖基化终末产物关键活性成分羧甲基赖氨酸(CML)对泡沫细胞迁移能力的影响。方法 RAW264.7单核巨噬细胞制备成荷脂细胞后,分为对照组、氧化型低密度脂蛋白(oxLDL)组和干预组(CML+oxLDL孵育)。采用Boyden小室细胞迁移实验体外观察泡沫细胞跨膜迁移能力,胆固醇氧化酶法检测细胞内游离胆固醇(FC)、胆固醇酯(CE)及总胆固醇(TC)的含量;RT-PCR和Western blot法检测清道夫受体CD36表达的变化。结果与oxLDL组比较,干预组细胞内FC、CE和TC持续增多(P<0.05),CD36mRNA与蛋白表达显著上调,迁移泡沫细胞荧光强度下调59.79%(P<0.05);与对照组比较,干预组迁移泡沫细胞荧光强度下调73.46%(P<0.05)。结论 CML可能通过与oxLDL的协同,触发CD36级联信号,抑制泡沫细胞迁移。     

趋化因子CXC配体16的生物学效应研究进展

能与磷脂酰丝氨酸和氧化型低密度脂蛋白结合的清道夫受体和趋化因子CXC配体16是同一种基因的不同命名。该蛋白质属于CXC家族,主要在抗原呈递细胞、平滑肌细胞、内皮细胞和T细胞中表达。作为清道夫受体,它以跨膜结合型存在,能与氧化型低密度脂蛋白结合。可能参与了巨噬细胞源性泡沫细胞的形成,导致动脉粥样硬化。作为趋化因子,它以分泌型存在时,主要在免疫系统、中枢神经系统和肿瘤等方面起重要作用。     

肺炎衣原体通过上调清道夫受体A1诱导THP-1源性泡沫细胞形成

目的观察清道夫受体A1和CD36在肺炎衣原体诱导THP-1源性泡沫细胞形成中的作用。方法给予不同浓度的肺炎衣原体(1×105～1×106IFU)感染THP-1源性巨噬细胞0～72h。运用油红O染色观察细胞质内脂滴的变化,酶荧光学法检测细胞内胆固醇酯含量的变化。分别运用逆转录聚合酶链反应和Western-Blot检测清道夫受体A1和CD36的mRNA和蛋白表达。结果高浓度的肺炎衣原体(5×105和1×106IFU)感染负荷低密度脂蛋白的THP-1源性巨噬细胞48h后,细胞质内的脂滴明显增多,胆固醇酯占总胆固醇百分比明显增加(>50%)。在负荷低密度脂蛋白的THP-1源性巨噬细胞上,肺炎衣原体感染呈浓度和时间依赖性地上调道夫受体A1 mRNA和蛋白表达,但不影响CD36 mRNA和蛋白表达。结论清道夫受体A1表达上调是肺炎衣原体诱导THP-1源性泡沫细胞形成的机制之一,这可能为进一步阐明肺炎衣原体感染促进动脉粥样硬化发生发展提供一个新的理论依据。     

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.