自发性高血压大鼠心肌fas基因表达与左室肥厚关系探讨

目的 探讨自发性高血压大鼠（SHR）心肌fas表达及其与左室肥厚的关系。方法 自发性高血压大鼠（SHR）与正常血压大鼠各16号，尾套法测收缩压，逆转录-聚合酶边反应（RT-PCR）法测心肌fas mRNA表达。结果 与WKY相比，SHR心肌fas表达、左室重量指数(LVMI)均显著升高，且二者呈正相关。结论 自发性高血压大鼠早期心肌肥厚时心肌fas表达已经升高，可能参与后期心衰的发生。     

自发性高血压大鼠心肌fas基因表达与左室肥厚关系探讨

目的探讨自发性高血压大鼠(SHR)心肌fas表达及其与左室肥厚的关系. 方法自发性高血压大鼠(SHR)与正常血压大鼠各16只,尾套法测收缩压,逆转录-聚合酶链反应(RT-PCR)法测心肌fas mRNA表达.结果与WKY相比,SHR心肌fas表达、左室重量指数(LVMI)均显著升高,且二者呈正相关.结论自发性高血压大鼠早期心肌肥厚时心肌fas表达已经升高,可能参与后期心衰的发生.     

高血压大鼠心脏肥厚过程中心肌细胞凋亡心肌纤维化动态观察

目的 探讨SHR心脏肥厚进展阶段心肌细胞凋亡、心肌纤维化及左室重构特点及其相互关系。方法 分别采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记（TUNEL）、放射免疫测定及病理检查方法对16周、24周龄、32周龄SHR心肌细胞凋亡指数（APOI）、心肌胶原容积分数（VF）和心肌血管周围胶原面积（PVCA）、血浆和组织血管紧张素Ⅱ检测,并以同龄Wister大鼠作对照。结果 与同龄正常血压Wistar大鼠比较,SHR各周龄组收缩压明显增高、心脏肥厚指标心脏重量（HW）、左室重量（LVW）、左室重量指数（LVW/BW) 显著增加;各周龄组SHR心肌细胞APOI显著增加,各周龄组间无显著性差异;各周龄组SHR大鼠血浆、心肌组织Ang Ⅱ明显增高;24、32周龄SHR的CVF和PVCA显著增加;SHR心肌组织Ang Ⅱ分别与APOI、CVF呈显著正相关,APOI与CVF呈显著正相关。结论 心肌细胞凋亡与心肌纤维化参与SHR代偿性心脏肥厚阶段心脏重构病理过程,组织Ang Ⅱ是导致SHR代偿性心脏肥厚阶段心肌细胞凋亡与心肌纤维化的重要机制之一。     

复方丹参滴丸及其与福辛普利联用对自发性高血压大鼠左室肥厚的影响

目的探讨复方丹参滴丸(DSP)及其与福辛普利联用对自发性高血压大鼠(SHR)左室肥厚的影响.方法将48只8周龄雄性SHR随机分为6组:DSP小剂量组、DSP大剂量组、福辛普利组、DSP小剂量与福辛普利联用组、DSP大剂量与福辛普利联用组、SHRs对照组.6组分别干预8周后测大鼠尾动脉收缩压;局部心肌/血浆血管紧张素Ⅱ、血浆醛固酮浓度;左室肥厚指数.结果DSP可降低血浆AngⅡ、Ald及局部心肌AngⅡ浓度(P＜0.01或P＜0.05),并可进一步增强福辛普利的这一作用;与对照组比较DSP可明显减轻左室肥厚(P＜0.01或P＜0.05),与福辛普利联用时可进一步提高后者的抗左室肥厚效应.结论DSP及其与福辛普利联用具有拮抗SHR左室肥厚作用.     

氯通道阻滞剂尼氟灭酸对肥厚心肌心室有效不应期及心室颤动阈值的疗效

背景肥厚心肌离子通道的重塑容易发生恶性室性心律失常，钙激活氯通道的改变起着重要的作用，尼氟灭酸（NFA）是常用的钙激活氯通道的阻滞剂。目的不同剂量NFA对左室肥厚心肌心室有效不应期及心室颤动阈值的影响。方法32只10周龄雄性自发性高血压大鼠（SHR）随机分成非NFA处理组及3个NFA不同剂量（0．01，0．1，1．0μmol／kg．iv）处理组，每组8只，取8只雄性Wistar大鼠作为对照组，分别测定各组大鼠心率、动脉收缩压、心室有效不应期、心室颤动阈值及左室质量指数。结果1）SHR左室质量指数明显大于Wistar大鼠（P〈0．01）；2）NFA非处理组的心室颤动阈值明显小于对照组[（15．0±1．2）mAVS（26．4±1．5）mA，P〈0．01）；3）NFA浓度越大延长左室肥厚心肌的心室有效不应期越明显，提高左室肥厚心肌的心室颤动阈值越明显（P〈0．05），呈浓度依赖趋势；4）心室有效不应期与心室颤动阈值正相关，NFA的3个不同处理剂量与心室有效不应期或心室颤动阈值正相关。结论NFA可以延长左室肥厚心肌的心室有效不应期，提高左室肥厚心肌的心室颤动阈值。     

依那普利或氯沙坦对SHR左室肥厚和心肌纤维化的影响

目的:观察自发性高血压大鼠(SHR)左室肥厚和心肌纤维化各指标的改变,以及依那普利和氯沙坦的保护作用.方法:雄性SHR(n=30)自第10周始服用依那普利(20mg@kg-1@d-1),或氯沙坦(25mg@kg-1@d-1),或二者合用(依那普利10mg@kg-1@d-1,氯沙坦12.5mg@kg-1@d-1)至第16周,并以年龄、性别、数量配对的未治疗SHR和Wistar-kyoto(WKY)大鼠作对照.测定收缩压(SBP)、左室重量(LVM)以及左室重量指数(LVMI)和左室心肌胶原含量;计算机图象分析心肌细胞大小、心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA).结果:SHR的SBP、LVM、LVMI、心肌胶原含量、心肌细胞的横截面积、CVF和PVCA均显著高于WKY对照组(P＜0.001).SHR治疗组上述指标显著低于SHR未治疗组(P＜0.01),依那普利与氯沙坦之间无显著差别(P＜0.05).二者合用比单用依那普利或氯沙坦更有效(P＜0.05).结论:依那普利和氯沙坦可显著的降低血压、逆转SHR早期左室肥厚和心肌纤维化,而且二者合用在逆转左室肥厚和心肌纤维化方面效果更明显.     

高血压大鼠心脏肥厚过程中心肌细胞凋亡心肌纤维化动态观察

目的探讨SHR心脏肥厚进展阶段心肌细胞凋亡、心肌纤维化及左室重构特点及其相互关系.方法分别采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记(TUNEL)、放射免疫测定及病理检查方法对16周龄、24周龄、32周龄SHR心肌细胞凋亡指数(APOI)、心肌胶原容积分数(CVF)和心肌血管周围胶原面积(PVCA)、血浆和组织血管紧张素Ⅱ检测,并以同龄Wister大鼠作对照.结果与同龄正常血压Wistar大鼠比较,SHR各周龄组收缩压明显增高、心脏肥厚指标心脏重量(HW)、左室重量(LVW)、左室重量指数(LVW/BW)均显著增加;各周龄组SHR心肌细胞APOI显著增加,各周龄组间无显著性差异;各周龄组SHR大鼠血浆、心肌组织AngⅡ明显增高;24、32周龄SHR的CVF和PVCA显著增加;SHR心肌组织AngⅡ分别与APOI、CVF呈显著正相关,APOI与CVF呈显著正相关.结论心肌细胞凋亡与心肌纤维化参与SHR代偿性心脏肥厚阶段心脏重构病理过程,组织AngⅡ是导致SHR代偿性心脏肥厚阶段心肌细胞凋亡与心肌纤维化的重要机制之一.     

自发性高血压大鼠肥厚左室心肌组织微小RNA-1与缝隙连接蛋白43的改变

目的观察自发性高血压大鼠(SHR)肥厚左室心肌组织微小RNA-1(miRNA-1)、缝隙连接蛋白43(Cx43)表达的变化及其关系,以探讨高血压性心肌肥厚发生室性心律失常(VA)的分子机制。方法 10只17周龄雄性SHR大鼠做为左室肥厚组(LVH组),10只8周龄雄性SHR大鼠做为对照组,通过病理学、心肌细胞横径的测量、实时荧光定量聚合酶链反应、免疫组织化学法及western blotting检测等方法 ,比较两组大鼠左室心肌组织病理学改变、miRNA-1及Cx43蛋白表达。结果①与对照组比较,LVH组的收缩压、舒张压升高,左室质量指数及心肌细胞横径均明显增大(P均0.05);miRNA-1表达水平明显升高,以及Cx43蛋白表达水平降低(0.27±0.10vs0.60±0.13,P0.05);②LVH组大鼠左室心肌组织miRNA-1与Cx43蛋白的表达水平呈显著负相关(r=-0.661,P0.05)。结论 miRNA-1可能通过抑制Cx43表达而参与高血压LVH发生VA。     

维持性血液透析患者颈动脉硬化与左心室肥厚的相关分析

目的：研究维持性血液透析（MHD）患者颈动脉硬化程度与左心室肥厚的关系。方法：收集48例MHD患者性别，年龄，体重，身高，BMI及病程等一般临床资料；静脉血查血红蛋白（Hb），尿素氮，肌酐，白蛋白，前白蛋白，总胆固醇，三酰甘油（TG），高密度脂蛋白胆固醇（HDL-C），低密度脂蛋白胆固醇（LDL-C），C反应蛋白（CRP），彩色B型超声仪观测双侧颈总动脉、颈动脉分叉处及颈内动脉的解剖及血流动力学，包括斑块，血管内皮厚度（即内膜-中膜厚度，IMT）等，并用超声心动图测定患者心脏的左心室内径、左心房内径、左心室后壁厚度（LVPWT）、室间隔厚度、左心室射血分数等。结果：48例患者中有28例（58％）颈动脉斑块阳性，颈动脉斑块阳性组患者年龄大于颈动脉斑块阴性组（P〈0．01），TC（P〈0．01）、LDL-C（P〈0．05）、CRP（P=0．01）、颈动脉内．中膜厚度（CCA-IMT）（P〈0．01）及左室心肌质量指数（LVMI）（P〈0．001）明显高于颈动脉斑块阴性组。性别分布、透析时间、收缩压、舒张压、脉压、TG、及Hb两组间无明显差异。48例患者中有37例（77％）有左室肥厚，左室肥厚组患者收缩压、舒张压及脉压明显高于无左室肥厚组（P〈0．01）；左室肥厚组高血压的发生率及LVMI明显高于无左室肥厚组（P〈0．001），CCA-IMT明显高于无左室肥厚组（P〈0．05），颈动脉斑块发生率明显高于无左室肥厚组（P〈0．01），而Hb则明显低于无左室肥厚组（P〈0．01）。两组之间在性别年龄分布、透析时间、CRP则无明显差别。相关性分析显示，LVMI与收缩压和脉压高度相关（P〈0．001），与舒张压和CCA-IMT中度相关（P〈0．01），与Hb呈负相关（P〈0．01）。结论：MHD患者颈动脉硬化与左室肥厚关系密切，动脉硬化的治疗有可能预防和逆转MHD患者的左室肥厚。     

Apelin-13在自发性高血压大鼠心肌组织的表达及其与心肌肥厚和心功能的关系

目的观察Apelin-13在自发性高血压大鼠(SHR)心肌组织的表达改变,探讨其与心肌肥厚和心功能的关系。方法选取清洁级4周龄和20周龄雄性自发性高血压大鼠和WKY(Wistar-Kyoto)大鼠,按周龄及种属分为4组,每组8只。分别测定无创尾动脉血压及心脏质量指数;超声心动图和血流动力学系统评估心室重构和心功能;HE染色评价心肌细胞及排列情况。Western blot法检测心肌组织Apelin-13、APJ的蛋白表达。结果 1Apelin-13、APJ在SHR心肌组织中呈低表达(P0.05),20周龄SHR较4周龄SHR更明显(P0.05)。2 SHR的收缩压(SBP)、左心室舒张期末压(LVEDP)、心脏质量指数(HW/BW)、心室质量指数(LVW/BW)、舒张期室间隔厚度(IVSD)和左心室舒张期末后壁厚度(LVWPd)明显升高(P0.05),左心室舒张期末内径(LVEDd)、左心室射血分数(EF)、左心室短轴缩短率(FS)和左心室压力最大下降速率(-dp/dtmax)明显降低(P0.05);心肌细胞明显肥大、排列紊乱。20周龄SHR与4周龄SHR相比,上述指标改变更加明显(P0.05)。3心肌组织Apelin-13与IVSD、HW/BW、LVW/BW以及LVEDd、LVEDP呈负相关(P0.05),与EF、FS和-dp/dtmax呈正相关(P0.05)。结论 Apelin-13在SHR心肌组织中呈低表达,其与心肌肥厚指标呈负相关,与心功能呈正相关,提示其可能影响高血压的左心室心肌肥厚和心功能。     

Immunohistological patterns of myeloid antigens: tissue distribution of CD13, CD14, CD16, CD31, CD36, CD65, CD66 and CD67

Summary. A number of differentiation antigens on myeloid cells have been defined on the CD classification system by the four International Workshops on Human Leucocyte Differentiation Antigens. The distribution of eight of these antigens (CD13, CD14, CD16, CD31, CD36, CD65, CD66, CD67) have been studied in human tissues, with the aim of documenting their immunohistological patterns and their degree of myeloid restriction. CD13, the most widely distributed antigen, was found in skin, bile canaliculi, kidney and pancreas. CD14 was not restricted to monocytes and tissue macrophages, being also strongly expressed on dendritic reticulum cells. CD 16 was expressed on granulocytes and tissue macrophages (alveolar and Kupffer cells) and in the red pulp of the spleen. CD31 and CD36 gave a characteristic staining of vascular endothelium, corresponding to their identification as the platelet glycoproteins gp IIa and gp IV. Antibodies against the most recently defined myeloid antigens (CD65, CD66 and CD67) appeared to be more specific for myeloid differentiation than previously described 'myeloid antigens'.     

Uncoupling CD21 and CD19 of the B-cell coreceptor

Complement receptors (CRs) CD21 and CD35 form a coreceptor with CD19 and CD81 on murine B cells that when coligated with the B-cell receptor lowers the threshold of activation by several orders of magnitude. This intrinsic signaling role is thought to explain the impaired humoral immunity of mice bearing deficiency in CRs. However, CRs have additional roles on B cells independent of CD19, such as transport of C3-coated immune complexes and regulation of C4 and C3 convertase. To test whether association of CR with CD19 is necessary for their intrinsic activation-enhancing role, knockin mice expressing mutant receptors, Cr2^Δ/Δgfp, that bind C3 ligands but do not signal through CD19 were constructed. We found that uncoupling of CR and CD19 significantly diminishes survival of germinal center B cells and secondary antibody titers. However, B memory is less impaired relative to mice bearing a complete deficiency in CRs on B cells. These findings confirm the importance of interaction of CR and CD19 for coreceptor activity in humoral immunity but identify a role for CR in B-cell memory independent of CD19.     

急性脑梗死患者外周血CD4CD25 T细胞和CD4CD28~- T细胞的变化

目的探讨急性脑梗死患者外周血CD4CD25T细胞和CD4CD28-T细胞亚群的变化及意义。方法选择急性脑梗死患者22例(脑梗死组),另选取健康体检者18例(对照组);均采用流式细胞仪检测外周血CD4CD25T细胞和CD4CD28-T细胞占CD4T细胞比例。结果脑梗死组外周血CD4CD25T细胞/CD4T细胞比例明显低于对照组[(41.14±9.92)%vs(49.01±12.19)%,P<0.05],而CD4CD28-T细胞/CD4T细胞比例明显高于对照组[(19.93±15.60)%vs(11.96±8.60)%,P<0.05]。结论急性脑梗死患者外周血CD4CD25T细胞比例减少,而CD4CD28-T细胞升高,两者共同作用,可能在脑梗死发生、发展中起重要作用。调节T淋巴细胞亚群可能是脑梗死的潜在治疗靶点。     

Proliferation and apoptosis of human CD8(+)CD28(+) and CD8(+)CD28(-) lymphocytes during aging

It is commonly believed that the age-related decrease in the ratio CD28(+)/CD28(-) among CD8(+) T cells reflects replicative senescence of the lymphocytes. To verify this claim we measured the proliferation of CD8(+)CD28(+) and CD8(+)CD28(-) subsets by flow cytometry after PHA treatment of mononuclear lymphocytes from donors of different age, including centenarians. The fraction of CD28(+) cells decreases from ca. 80 to 40% (young to centenarians, respectively) with increasing age of the donors. Stimulation by PHA results in an increase in the ratio of CD28(+) relative to CD28(-) in all age groups. We found that not only CD8(+)CD28(+) but also CD8(+)CD28(-) cells were capable of proliferation. Moreover, the fraction of proliferation-competent CD28(-) cells was higher in the older donors compared with the younger ones. While PHA treatment led to apoptosis (as measured by DNA content and caspase-3 activation) of more than 20% of all lymphocytes, in the CD8(+) subset only ca. 10% died, irrespective of their CD28 status. Altogether, we showed over-representation of proliferating CD8(+)CD28(-) cells in aged people, which might not be particularly prone to undergo apoptosis.     

Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides

OBJECTIVE: To assess circulating immunoregulatory cytokines and soluble surface markers of T and B cell activation in the plasma of patients with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA) during active and inactive disease, in order to establish their value in discriminating between disease entities and as markers of disease activity. METHODS: Plasma levels of IL-4, IL-5, IL-10, IL-12, IL-13, IFN-gamma and soluble CD23, CD26 and CD30 were determined by enzyme-linked immunosorbent assay in patients with WG (n = 21), CSS (n = 19) and MPA (n = 14) during active disease and remission. RESULTS: Concerning cytokines, no differences were observed for IFN-gamma, IL-4, IL-5 and IL-13. Plasma levels of IL-12 were decreased in all subgroups of patients. On the contrary, IL-10 levels were significantly elevated only in patients with CSS. Levels of sCD30 were significantly increased in patients with active generalized WG and CSS, but not in those with MPA and localized WG, correlating with the disease extent and activity. sCD26 levels were markedly decreased in patients with generalized WG, CSS and MPA and increased towards remission. sCD23 levels were slightly, but not significantly increased in CSS and generalized WG. CONCLUSION: Regarding the investigated immunoregulatory cytokines (Th1/Th2 type), only the measurement of plasma levels of IL-10 discriminated CSS from WG and MPA. The reported data could indicate a similar status of T cell activation in generalized WG and CSS, and possibly a shift in peripheral immunity towards a more humoral dominated immune response. The differences observed between patients with the localized and generalized forms of WG seem to reflect the clinically known biphasic course of this disease.     

CD133和CD90在肝细胞癌中的表达及其意义

存在于肿瘤组织中的少数具有干细胞性质的细胞群体被称为肿瘤干细胞(CSCs),可促进肿瘤的发生和发展,也是肿瘤耐药性、复发及转移的根源.有报道CD133和CD90可能为肿瘤干细胞表面标志物,但CD133和CD90在肝癌中的表达及其意义报道尚少.本研究采用免疫组织化学方法检测不同肝组织中CD133及CD90蛋白的表达水平,探讨其在肝癌中的表达情况及其与肝癌生物学特性及预后的关系.     

Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.     

Differential CD26-mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation

Patients who have undergone allogeneic bone marrow transplantation (allo-BMT) are susceptible to a variety of opportunistic infectious complications in the months to years after engraftment. Impaired in vitro T-cell functions have been documented in these patients, and these T-cell dysfunctions contribute to the prolonged immune deficiency after allo-BMT. In the present study, we examined the expression of CD26 as well as the reconstitution of CD26-mediated T-cell costimulation via the CD3 and CD2 pathways at various times in patients aged greater than 18 years after CD6-positive, T-cell depleted allo- BMT. We found that the percentage of CD26- and CD3-positive cells, as well as the levels of expression of both antigens, was lower than in normal controls during the first 4 months after CD6-depleted allo-BMT. Subsequently, the amount of lymphocytes expressing CD3 and CD26 and the quantitative surface expression of CD3 and CD26 were not significantly different in patients and normal controls. Functional studies showed that CD26-mediated T-cell proliferation via the CD3 pathway was considerably improved and almost reached normal levels by 1 year, whereas recovery of CD26-mediated T-cell proliferation via the CD2 pathway was delayed for at least 2 years after CD6-depleted allo-BMT. As CD26 involvement in the regulation of human thymocyte activation is restricted preferentially to the CD3 pathway--unlike its involvement with both CD3 and CD2 pathways of peripheral T cells--our results suggest that the different effects of CD26-mediated costimulation via the CD3 and CD2 pathways after CD6-depleted allo-BMT may be a reflection of peripheral T-cell immaturity in those individuals, similar to that seen in mature medullary thymocytes or cord T lymphocytes.