醒后卒中和发病时间不明卒中的再灌注治疗

醒后卒中和发病时间不明卒中因发病时间不确定而往往被排除在溶栓治疗之外.然而,许多临床研究显示,多模式影像学技术可有效指导醒后缺血性卒中和发病时间不明卒中患者进行静脉溶栓,其血管内治疗也取得了一定的进展.文章主要对醒后卒中和发病时间不明卒中患者的影像学表现、静脉溶栓和血管内治疗进行了综述.     

心房颤动对静脉溶栓治疗急性缺血性卒中转归的影响

目的 探讨心房颤动(atrial fibrillation,AF)对急性缺血性卒中患者静脉溶栓后临床转归和出血性转化(hemorrhagic transformation,HT)的影响.方法 回顾性纳入接受静脉重组组织型纤溶酶原激活剂溶栓治疗的急性缺血性卒中患者.90 d时改良Rankin量表评分0～2分定义为转归良好.采用多变量logistic回归分析确定AF与静脉溶栓后临床转归的相关性.结果 共纳入160例接受静脉溶栓治疗的急性缺血性卒中患者,其中67例(41.88％)合并AF.与非AF组相比,AF组年龄更大[中位数和四分位数间距:77(71 ～83)岁对69(59 ～78)岁;Z=4.142,P＜0.001],基线美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NHISS)评分更高[11(6～17)分对7(4 ～14)分;Z=2.623,P=0.009].AF组溶栓后24 h[3.0(1.0～4.5)分对2.0(0～6.0)分;Z=-0.312,P=0.775]和7 d[4.0(2.0～5.0)分对5.0(2.0～8.0)分;Z=1.574,P=0.115]时NIHSS评分较基线降低值以及90 d时转归良好患者比例(38.81％对25.82％;x2 =3.063,P=0.080)与非AF组差异均无统计学意义,但24 h内HT(14.93％对5.38％;x2=4.179,P=0.041)和90 d内死亡(16.42％对6.45％;x2 =4.073,P=0.044)患者比例显著高于非AF组.多变量logistic回归分析显不,AF与90 d时临床转归[优势比(odds ratio,OR0.95,95％可信区间(confidence interval,CI)0.381～2.366;P=0.912]、24 h内HT(OR1.992,95％ CI 0.580 ～6.369;P=0.285)以及90 d内死亡(OR 2.483,95％ CI0.727～8.586;P=0.146)均无独立相关性.结论 AF不是影响急性缺血性卒中患者静脉溶栓后90 d时临床转归和24 h内HT的独立危险因素.     

Impact of proteolytic enzymes in colorectal cancer development and progression

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.     

还脑益聪方对早期认知功能障碍大鼠血浆P-选择素、血浆纤溶酶原激活物抑制剂和血液流变学指标的影响

目的观察中药复方还脑益聪方对复合因素所致早期认知功能障碍大鼠行为学及血浆P-选择素、血浆纤溶酶原激活物抑制剂（PAI-1）和血液流变学指标的影响。方法采用皮下注射D-半乳糖及喂饲半高脂饲料（6周）的方法造成大鼠认知功能障碍,Morris水迷宫行为学测试确定模型成功的动物,随机分成四组（每组12只）：模型对照组给予等量水,盐酸多奈哌齐（hydrochloricdonepezil）组（0．4mg／kg,体质量,下同）,还脑益聪方低剂量组（7g生药／kg）,还脑益聪方高剂量组（14g生药／kg）,同时灌胃给药,并设立正常对照组,给予等量水。4周后,对大鼠行为学检测,应用酶联免疫法（ELISA法）检测大鼠血浆P-选择素及PAI-1含量和血液流变学各项指标。结果与正常对照组大鼠比较,造模后大鼠水迷宫测试,潜伏期显著延长（P〈0．05）,寻台路程明显延长和穿台次数显著减少（P〈0．01）,存在空间学习记忆能力减退。同时,血清P-选择素含量和PAI-1含量显著升高（P〈0．05,P〈0．01）,血液黏度及血小板聚集性增加（P〈0．05,P〈0．01）等流变学指标改变。与模型组比较,还脑益聪方高剂量组可增加大鼠穿台次数和减少寻台路程（P〈0．01）,降低P·选择素及PAI-1的含量（P〈0．05）,降低低剪切率下的血液黏度（P〈0．05,P〈0．01）,降低红细胞聚集指数（P〈0．01）和血浆纤维蛋白原（FDP）含量（P〈0．05）。结论还脑益聪方对D-半乳糖及半高脂饲料造成的大鼠认知功能障碍有明显的改善作用,显著提高动物的空间学习记忆能力,并能抑制大鼠P-选择素和PAI-1水平,改善血液的流变性。     

纤溶酶原激活剂抑制物-1基因4G/5G多态性与特发性卵巢早衰的相关性

目的:探讨纤溶酶原激活剂抑制物-1(plasminogen activator inhibitor-1,PAI-1)基因启动子区4G/5G多态性与特发性卵巢早衰(premature ovarian failure,POF)发病的关系。方法:应用PCR-RFLP分析,检测65例特发性POF患者(POF组)和75例正常妇女(对照组)PAI-1基因4G/5G多态性。结果:特发性POF患者组PAI-1基因型频率分布,4G/4G型为29.2%,4G/5G型为55.4%,5G/5G型为 15.4%;POF患者组4G/4G基因型频率明显高于对照组(16.0%),但差异无显著性意义(x2=3.54,P>0.05);而4G等位基因频率(0.569)显著高于对照组(0.447)(x2=4.18,P<0.05),携带4G等位基因个体发生特发性POF的相对风险OR= 1.64,95%CI1.02～2.64。结论:PAI-1基因4G/5G多态性与特发性POF的发病有关,4G等位基因可能是特发性POF发病的危险因素之一。     

纤溶酶原激活物抑制因子-1对肝星状细胞转化生长因子β1、透明质酸、基质金属蛋白酶抑制因子-1的影响

目的 探讨外源性纤溶酶原激活物抑制因子-1(PAI-1)对人肝星状细胞(HSC)转化生长因子β1(TGFβ1)、基质金属蛋白酶抑制因子-1(TIMP-1)及透明质酸(HA)表达的影响.方法 培养液中加入PAI-1,采用四甲基偶氮唑盐法检测人HSC株LX-2的增殖变化,确定PAI-1的最佳干预浓度.将LX-2培养液中加入PAI-1分别培养12、24、48 h,采用酶联免疫吸附法(ELISA)检测细胞上清液中TGFβ1、TIMP-1及HA的变化.结果 阴性对照组A492为0.473±0.035;PAI-1浓度为5、10、20、40、80μg/L时,A492分别为1.249±0.440、1.636±0.315、1.283±0.413、0.938±0.263、0.303±0.125,PAI-1浓度为10μg/L时刺激作用最为明显(F=11.697,P＜0.01).加入PAI-1培养12、24、48 h组较阴性对照组细胞上清液中TGFβ1、HA及TIMP-1表达增加(F=1566.752、P＜0.01,F=235.632、P＜0.01,F=67.359、P＜0.05).结论 PAI-1可促进肝星状细胞TGFβ1、TIMP-1及HA的表达,从而影响肝纤维化的发生发展.

Abstract：

Objective To study the effect of plasminogen activator inhibitor type-1 ( PAI-1 ) on the protein expression of transforming growth factor-beta 1 ( TGFβ1 ), hyaluronic acid ( HA ) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of hepatic stellate cells(HSC). Methods Methyl thiazolyl tetrazolium (MTT)was performed to detect the effect of PAI-1 on the proliferation of LX-2 ,and to determine the perfect intervention concentration of PAI-1. After incubation with PAI-1 in LX-2 culture solution for 12 h,24 h,48 h,the protein expression of TGFβ1 ,TIMP-1 and HA was observed with enzyme linked immunosorbent assay (ELISA). Results A492 in the negative control was 0. 473 ± 0. 353, and 1. 249 ± 0. 440, 1. 636 ± 0. 315,1.283 ± 0. 413,0. 938 ±0. 263 and 0. 303 ±0. 125 when the concentration of PAI-1 was 5,10,20,40 and 80 μg/L,respectively,a concentration of 10 μg/L of PAI-1 showed the strongest stimulation remarkablely ( F = 11. 697, P ＜ 0. 01 ).After incubation with PAI-1 for 12 h,24 h,48 h,the protein expression of HA,TGFβ1 and TIMP-1 in the LX-2 supernatant significantly increased compared to negative control (F = 1566. 752,235. 632 and 67. 359,respectively,P ＜ 0. 01 or ＜ 0. 05 ). Conclusion PAI-1 may influence the development of hepatic fibrosis through promoting the protein expression of HA ,TGFβ1 and TIMP-1 of HSC.     

Angiotensin converting enzyme DD genotype affects the changes of plasma plasminogen activator inhibitor-1 activity after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction patients

Angiotensin converting enzyme (ACE) DD genotype, and plasminogen activator inhibitor (PAI-1) 4G/4G genotype have been reported to affect PAI-1 activity in control subjects and atherosclerotic patients, but no data are available on the influence of angiotensin II type 1 receptor (AT1R) A1166C polymorphism on the inhibitor levels. The degree of fibrinolytic activation after percutaneous transluminal coronary angioplasty (PTCA) has been found to affect the risk of restenosis. The aim of this study was to investigate the possible influence of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms on the changes of PAI-1 activity after primary successful percutaneous transluminal angioplasty. In 29 consecutive acute myocardial infarction patients, undergoing primary successful angioplasty, genotyping of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis, and PAI-1 plasma activity (chromogenic method) was assessed before and after angioplasty. Following angioplasty, PAI-1 activity increased in 10 of 29 patients and decreased or remained unchanged in 19 of 29. ACE DD genotype was significantly (P = 0.04) associated with an increase of PAI-1 activity post angioplasty (OR DD/ID+II = 6.5, CI 95% 4.83-8.22). Whereas no effect of PAI-1 4G/5G and AT1R A1166C polymorphisms on PAI-1 response to angioplasty was demonstrated, these data suggest that renin-angiotensin system genes are involved in the regulation of the fibrinolytic response to balloon injury, possibly affecting angiotensin converting enzyme activity. This interaction between the renin-angiotensin system and hemostasis may be a mechanism by which ACE DD genotype affects the risk of restenosis after percutaneous transluminal angioplasty.     

活血化瘀药物对肝癌细胞HepG2的抑制作用及机制

目的观察活血化瘀中药在体外实验条件下对人肝癌细胞HepG2细胞增殖、迁移的影响,对纤溶酶原激活物抑制剂-1（PAI-1）表达的影响,探讨活血化瘀药物对人肝癌细胞HepG2细胞的抑制作用与分子机制。方法培养HepG2细胞,将中药黄芪、复方当归、复方丹参、川芎嗪分别加入体外培养的肝癌细胞株HepG2细胞,应用MTS法检测其对人肝癌细胞HepG2细胞增殖的影响;应用细胞迁移实验观察其对HepG2细胞迁移的影响;应用RT—PCR方法检测对HepG2细胞PAI-1mRNA表达的影响,ELISA法检测对PAI-1表达的影响。结果活血化瘀中药黄芪、当归、丹参、川芎嗪可不同程度地抑制HepG2细胞增殖与迁移,降低HepG2细胞PAI-1mRNA表达、抗原水平,以复方丹参、川芎嗪组作用更为明显。结论活血化瘀中药可有效抑制人肝癌细胞HepG2细胞增殖与迁移,同时抑制PAI-1表达,这可能是其具有抗肿瘤作用的分子机制之一。     

纤溶酶原激活物抑制物1与肝细胞癌

目的研究纤溶酶原激活物抑制物１（ＰＡＩ１）在肝细胞癌（ＨＣＣ）蛋白和ｍＲＮＡ水平的表达及其与ＨＣＣ生物学特性的关系。方法取ＨＣＣ石蜡标本４８例,肝良性肿瘤石蜡标本１２例（对照组）做免疫组化染色;液氮冻存ＨＣＣ标本２０例,肝血管瘤５例（对照组）做免疫印迹杂交。结果肝癌细胞与癌周细胞及对照组肝细胞相比,ＰＡＩ１抗原蛋白和ｍＲＮＡ表达显著升高,差异有显著意义,Ｐ值分别＜００１和＜０．０５。术后２年内死亡病例与生存病例相比,ＰＡＩ１阳性率有显著意义的升高,Ｐ＜００５。ＰＡＩ１和纤溶酶原激活物（ｕＰＡ）及其受体（ｕＰＡＲ）同时阳性患者与同时阴性患者相比,前者侵袭性病例较后者升高有显著性意义（Ｐ＜００５）。结论ＨＣＣ中ＰＡＩ１蛋白和ｍＲＮＡ表达明显增高。ＰＡＩ１与ＨＣＣ浸润转移和预后密切相关。     

丹参注射液对血管紧张素Ⅱ诱导系膜细胞PAI-1表达和ROS含量的影响

目的观察丹参注射液对血管紧张素Ⅱ（AngⅡ）诱导系膜细胞纤溶酶原激活物抑制物1（PM-1）表达和活性氧（ROS）含量的影响,探讨丹参注射液抗肾小球硬化的机制。方法将培养的大鼠系膜细胞分为未干预组（N组）、AngⅡ-Ⅲ激组（A组,AnglI浓度为100nmol／L）、AngⅡ＋丹参干预组（按照丹参注射液浓度分为S1、S2和S3组,丹参注射液浓度分别为37．5g／L、75g／L和150g／L）以及单独丹参干预组（S组,丹参注射液浓度为150g／L）。S1、S2和岛组加入丹参注射液作用1h后,再加入AngⅡ（浓度为100nmol／L）共孵育24h。观察各组系膜细胞PAI-1mRNA和蛋白表达以及细胞ROS含量的变化。结果与N组相比,A组PAI-1mRNA和蛋白表达升高（P〈0．01）,S组PAI-1 mRNA和蛋白表达无差异（P〉0．05）;与A组相比,S1、S2、S3组PAI-1mRNA和蛋白表达降低（P〈0．01）。与N组相比,A组细胞R0s含量升高（P〈0．01）,S组细胞ROS含量无差异（P〉0．05）;与A组相比,S1组细胞ROS含量无差异（P〉0．05）,S2、s3组细胞ROS含量降低（P〈0．01）。结论AngⅡ通过刺激系膜细胞产生致肾纤维化因子,丹参注射液能抑制这些因子的产生。