p38丝裂素活化蛋白激酶介导自发性高血压大鼠血管平滑肌细胞增殖

目的研究p38丝裂素活化蛋白激酶(p38MAPK)信号传导通路在血管紧张素Ⅱ(AngⅡ)与血小板源性生长因子-BB(PDGF-BB)诱导的自发性高血压大鼠(SHR)血管平滑肌细胞(VSMC)增殖中的作用。方法本实验采用体外培养SHR胸主动脉平滑肌细胞,用3H-胸腺嘧啶核苷([3H]-TdR)掺入法测定细胞增殖状况。用特异性的Phospho-p38MAPK抗体的蛋白免疫印迹法(Westernblot)检测p38MAPK的活性。结果1)AngⅡ、PDGF成剂量依赖性促进SHR血管平滑肌细胞[3H]-TdR掺入率,当AngⅡ为10-7mol/L、PDGF为10ng/L时,[3H]-TdR掺入率显著增加[AngⅡ组:(11588±1322)比对照组(2546±207)计数/min;PDGF:(5279±391)比对照组(2587±230)计数/min,P<0.05]。p38MAPK选择性阻断剂SB202190(10-9～10-7mol/L)呈浓度依赖性地降低AngⅡ、PDGF诱导的VSMC增殖活度。2)AngⅡ、PDGF对p38MAPK的磷酸化均有显著增强作用,此作用同样被SB202190抑制。3者作用都呈剂量依赖性。结论AngⅡ、PDGF能激活SHR血管平滑肌细胞的p38MAPK发生磷酸化,进而导致血管平滑肌细胞增殖。     

血管紧张素Ⅱ诱导自发性高血压大鼠血管外膜成纤维细胞迁移活性涉及P38 MAPK

目的研究血管紧张素Ⅱ(AngⅡ)诱导自发性高血压大鼠(SHR)血管外膜成纤维细胞迁移活性的变化及该过程是否涉及P38MAPK信号途径。方法用Transwell Chamber观察AngⅡ诱导的血管外膜成纤维细胞的迁移活性,及AT1受体拮抗剂氯沙坦、P38MAPK特异性的抑制剂SB202190对AngⅡ诱导的迁移活性的影响。进一步用免疫印迹技术观察AngⅡ诱导后P38MAPK的磷酸化,及氯沙坦、SB202190对P38MAPK磷酸化的影响。结果AngⅡ诱导SHR大鼠血管外膜成纤维细胞迁移活性较WKY大鼠显著增高,且呈剂量依赖性。氯沙坦及SB202190能抑制AngⅡ诱导的迁移活性。AngⅡ诱导SHR外膜成纤维细胞P38MA：PK的磷酸化,呈剂量和时间依赖性;该作用能够被氯沙坦、SB202190抑制。结论AngⅡ诱导SHR大鼠血管外膜成纤维细胞迁移活性增强,该过程涉及P38MAPK信号途径。     

血管紧张素Ⅱ对人脐静脉内皮细胞p38丝裂素激活蛋白激酶通路的作用

目的探讨血管紧张素Ⅱ(AngⅡ)激活人脐静脉内皮细胞(HUVECs)p38丝裂素激活蛋白激酶(p38MAPK)信号转导通路的作用。方法用含20%胎牛血清的DMEM培养基与CO_2培养箱(5%CO_2+95%空气)培养HUVECs。待细胞生长至80%融合时,无血清培养16h后分组:(1)AngⅡ不同时点观察组:用AngⅡ(终浓度100 nmol/L)分别刺激细胞0、5、10、15、30、45 min和60 min。(2)AngⅡ不同剂量作用组:分别用终浓度为0、10、100、1000 nmol/L和10 000 nmol/L的AngⅡ刺激细胞15 min。(3)AngⅡ+p38MAPK特异性抑制剂SB202190组:在AngⅡ(终浓度100 nmol/L)刺激前30 min,分别将1000 nmol/L和5000 nmol/L(终浓度)的SB202190加入培养基,共同孵育30 min。上述各组作用一定时间后收集细胞,用Western blot方法测定细胞p38MAPK磷酸化表达。结果 AngⅡ(100 nmol/L)可诱导HUVECs p38MAPK磷酸化表达,15～30 min达到高峰,分别升高2.25和2.51倍(P<0.005,n=5),随时间呈峰形变化;AngⅡ呈剂量依赖性诱导HUVECs p38MAPK磷酸化,在AngⅡ100 nmol/L时p38MAPK磷酸化表达即有明显增强,在AngⅡ刺激剂量为1000 nmol/L和10 000 nmol/L时,p38MAPK磷酸化表达分别增加2.03和2.11倍(P<0.005,n=5);p38MAPK特异性抑制剂SB202190可显著抑制HUVECs p38MAPK磷酸化,且呈剂量依赖性,5000 nmol/L SB202190的抑制率为53.9%(P<0.01,n=6)。结论 AngⅡ可激活人脐静脉内皮细胞p38MAPK信号通路。     

血管紧张素-(1-7)对人脐动脉平滑肌细胞p38MAPK通路的抑制作用

目的 探讨血管紧张素-(1-7)[Ang-(1-7)]阻断血管紧张素Ⅱ(AngⅡ)致炎作用的可能机制.方法 用DMEM培养基培养血管平滑肌细胞(VSMCs),待细胞生长至80％融合时无血清培养12小时后分为两组:Ⅰ组:对照组、AngⅡ组、Ang-(1-7)组、AngⅡ+Ang-(1-7)组、AngⅡ+ Ang-(1-7)+ A-779组、A-779组;Ⅱ组:对照组、AngⅡ组、AngⅡ+不同浓度Ang-(1-7)组.上述两组作用一定时间后收集细胞,用Western blot方法测定细胞p38丝裂原活化蛋白激酶(p38MAPK)蛋白磷酸化表达.结果 Ang-(1-7)(1000 nmol/L)可拮抗AngⅡ(100 nmol/L)诱导的VSMCs p38MAPK磷酸化表达,且呈剂量依赖性,随着Ang-(1-7)剂量的增加,p38MAPK磷酸化表达逐渐减弱.结论 Ang-(1-7)呈剂量依赖性抑制AngⅡ激活人脐动脉平滑肌细胞p38MAPK通路的作用,从而可能拮抗AngⅡ的致炎作用.     

肾上腺髓质素抑制血管紧张素Ⅱ刺激血管平滑肌细胞增生作用

目的　观察肾上腺髓质素 (adrenomedullinADM)对血管紧张素Ⅱ (AngⅡ )刺激血管平滑肌细胞增生作用的影响。方法　测定ADM、AngⅡ对细胞3H leu掺入及 (MAPK)和 (PKC)活性的作用。结果　AngⅡ促进细胞3H leu掺入及MAPK和PKC活性增加 ;ADM对细胞3H leu掺入及MAPK、PKC活性均无明显影响 ,但呈浓度依赖方式抑制AngⅡ促细胞3H leu掺入及MAPK活性增加。结论　ADM通过抑制AngⅡ对MAPK的激活 ,拮抗其促血管平滑肌细胞增生作用。     

丝裂素活化蛋白激酶的激活和转核与大鼠 血管平滑肌细胞增殖关系的研究

目的 探讨丝裂素活化蛋白激酶（MAPK）激活、转核与血管紧张素Ⅱ（AngⅡ)刺激血管平滑肌细胞（VSMC）增殖间的关系。方法 本实验采用培养大鼠胸主动脉VSMC。用^3H-胸腺嘧啶核苷（^3H-TdR)掺入法测定DNA合成,用p43/p44磷酸化抗MAPK抗体的蛋白免疫印迹法测定MAPK蛋白量,用免疫细胞化学技术观察MAPK活化并转位入细胞核的过程。结果 （1）AngⅡt和PD98059的上述作用都呈剂量依赖性。（2）AngⅡ对MAPK蛋白表达有显著增强作用。此作用同样被PD98059以剂量依赖方式抑制。（3）AngⅡ刺激5min后,MAPK出现在VSMC的细胞浆中,30min时MAPK进入细胞核,3h后MAPK染色从核内消失,上述MAPK转核过程被PD98059抑制。结论 本实验证实人细胞核,3h后MAPK染色从核人消失,上述MAPK转核过程被PD98059抑制。结论 本实验证实AngⅡ能激活培养大鼠主动脉VSMC的MAPK,活化的MAPK从细胞浆转位进入细胞核导致VSMC增殖。     

p38MAPK介导PDGF-BB诱导的大鼠血管平滑肌细胞MMP-2基因表达

目的　观察血小板源性生长因子BB（PDGF-BB）是否可以诱导大鼠血管平滑肌细胞（VSMC）基质金属蛋白酶2（MMP-2）基因表达及VSMC的迁移,探讨p38信号通路在这一过程中的作用,为血管重建性疾病的研究提供实验依据。方法　PDGF-BB不同浓度和不同时间刺激体外培养的大鼠VSMC,用放线菌素D、SB202190（MAPK/p38特异性抑制剂）处理PDGF-BB诱导的VSMC。细胞划痕实验检测细胞迁移,运用Real-time　RT-PCR检测MMP-2基因表达水平,Western　blot　检测p38的活性变化。结果　PDGF-BB可促进VSMC迁移,SB202190可抑制PDGF-BB诱导的VSMC迁移。不同浓度PDGF-BB（10　μg/L～50　μg/L）作用VSMC　0.5　h,MMP-2基因表达明显增加,其中以20　μg/L较显著;用20　μg/L　PDGF-BB作用VSMC　0.5　h～4　h,可显著上调MMP-2基因表达,以0.5　h较显著。用放线菌素D和SB202190预处理后MMP-2基因表达降低。PDGF-BB可激活VSMC中磷酸化p38水平,SB202190可抑制　p38的磷酸化以及相应的MMP-2基因表达。结论　p38参与了PDGF-BB诱导的VSMC迁移及MMP-2基因表达。     

酪氨酸蛋白激酶抑制剂对自发性高血压大鼠血管平滑肌细胞增殖肥大的影响

为明确自发性高血压大鼠血管平滑肌细胞（SHR－VSMC）增殖与血小板源生长因子－AA（PDGF－AA），PDGF-α受体表达的关系及酪氨酸蛋白激酶在其中的作用，我们在培养的血管平滑肌细胞中，采用免疫印迹（western blot)3H-TdR及3H－Leu掺入等方法，观察在不同来源大鼠（SHR／Wistar)血管平滑肌细胞中，PDGF－AA，PDGF－α受体及PDGF－β受体表达的差异性；在PDGF－AA刺激下细胞的增殖，肥大反应及酪氨酸蛋白激酶抑制剂(genistein)对其的影响，结果表明，在SHR－VSM中PDGF－AA，PDGF－α受体蛋白表达明显高于Wistar-VSMC，而DGF－β受体蛋白表达在SHR－VSMC与Wistar-VSMC无明显差异，在不同浓度PDGF－AA（2、5、10、20)ng/ml刺激下，SHR－VSMC中PCNA表达呈剂量依赖性增高P＜0．01，加入酪氨酸激酶抑制剂，SHR－VSMC中PCNA表达呈剂量依赖性显著减少P＜0．01，在不同浓度PDGF－AA（2、5、10、20）ng/ml刺激下，SHR－VSMC中3H－Leu,3H-TdR掺入率呈剂量依赖性增强；加入酪氨酸激酶抑制剂SHR－VSMC中3H－Leu,3H-TdR掺入率显著减少，PDGF与其受体结合后，可激活受体细胞膜内的酪氨酸蛋白激酶，导致蛋白分子磷酸化的级联反应，启动MAPK，PKC等信号转导通路，调节特定基因的表达或通过改变细胞内相应蛋白质的功能状态导致细胞的增殖肥大，本实验应用酪氨酸激酶抑制剂genistein阻断酪氨酸激酶活性，证实阻断PDGF－AA所介导的自发性高血压大鼠血管平滑肌细胞增殖肥大，关键是阻断酪氨酸蛋白激酶的活性，酪氨酸蛋白激酶介导的信号转导在其中发挥重要作用。β     

血管紧张素（1-7）对血管紧张素Ⅱ激活人脐静脉内皮细胞p38MAPK通路的拮抗作用

目的 探讨血管紧张素(1-7)[Ang-(1-7)] 阻断血管紧张素Ⅱ(AngⅡ)致炎作用的可能机制.方法 原代培养人脐静脉内皮细胞,取2～5代用于实验.培养细胞随机分两组:Ⅰ组:对照组,AngⅡ组和AngⅡ+不同浓度Ang (1-7)组;Ⅱ组:对照组,AngⅡ组,Ang (1-7)组,AngⅡ+Ang-(1-7)组,AngⅡ+Ang (1-7)+A-779组,A-779组.用免疫印迹法测定细胞p38MAPK磷酸化表达.培养细胞用RT-PCR法测定Ang(1-7)的特异性受体Mas受体的表达.结果 100 nmol/L Ang(1-7)可以拮抗100 nmol/L AngⅡ诱导的人脐静脉内皮细胞p38MAPK磷酸化表达,且呈剂量依赖性.随着Ang(1-7)剂量的增加p38MAPK磷酸化表达逐渐减弱,在1000 nmol/L Ang(1-7)时即有明显减弱.Ang(1-7)受体特异性拮抗剂A-779可显著抑制Ang(1-7)的此作用.结论 Ang(1-7)呈剂量依赖性拮抗AngⅡ激活人脐静脉内皮细胞p38MAPK通路的作用.     

血管紧张素Ⅱ、内皮素对SHR主动脉平滑肌细胞增殖的作用

目的:探讨血管紧张素Ⅱ(AngⅡ)、内皮素(ET-1)对SHR、WKY VSMC增殖的作用.方法:贴块法培养SHR、WKY VSMC,用　3H-TdR参入和细胞计数反映VSMC增殖情况.结果:SHR、WKY VSMC 　3H-TdR参入随AngⅡ、ET-1浓度的增加而增加,呈剂量依赖性.10-7mol/L AngⅡ、ET-1使SHR VSMC　3H-TdR参入提高到对照组的1.9、2.7倍,WKY VSMC 　3H-TdR参入提高到对照组的1.3、1.6倍.AngⅡ不促使SHR、WKY VSMC增生.10-7mol/L ET-1分别使SHR、WKY VSMC细胞数增加209±27%、97±13%.10-7mol/L AngⅡ和ET-1则使SHR、WKY VSMC　3H-TdR参入提高到对照组的7.0、4.2倍,细胞数增加3.0、1.3倍.结论:AngⅡ、ET-1对VSMC的增殖有协同效应.高血压时,VSMC对促生长因子敏感性增加,更易发生肥大增殖.     

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.     

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.     

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.     

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.