心肌缺血预适应对缩小心肌梗塞范围的临床研究

近年动物试验证明心肌缺血预适应有一种保护作用。本组分析了近３年我院急性前壁心肌梗塞１１０例病人缺血预适应对心肌梗塞的影响。其中男７７例，女３３例。心肌梗塞前有预缺血者６９例（Ａ组）．，无预缺血者４１例（Ｂ组）。资料分析显示：Ｂ组心肌梗塞时心肌坏死范围、心肌酶峰值、心功能损害、室壁瘤形成及死亡率均高于Ａ组，两组差异有显著性。还就心肌缺血预适应发生时间及其对心肌保护作用之间的关系，缺血预适应的可能机制及临床意义进行了讨论。     

心肌缺血预适应对老年急性心肌梗塞近期预后的影响

本文分析８９例老年急性心肌梗塞（ＡＭＩ）病人心肌缺血预适应（ＭＩＰ）对其近期预后的影响，其中男５１例，女３８例，心肌梗塞前有ＭＩＰ者５８例（Ａ组），无ＭＩＰ者３１例（Ｂ组），资料分析显示，Ａ组在发生ＡＭＩ时，心肌坏死范围、心肌酶峰值、心功能损害、室性心律失常、心原性休克、室壁瘤形成及病死率均明显低于Ｂ组（Ｐ＜０．０５），两组有显著性差异，并对ＭＩＰ的临床意义和机理进行了讨论     

心肌缺血预适应对缩小老年心肌梗塞范围的临床研究

目的探讨心肌缺血预适应对老年急性心肌梗塞（ＡＭＩ）患者梗塞面积的影响。方法对照分析心肌梗塞前６６例有心肌缺血预适应与４４例无心肌缺血预适应老年ＡＭＩ患者的临床资料。结果有心肌缺血预适应老年ＡＭＩ患者其肌酸磷酸激酶（ＣＰＫ）与肌酸磷酸激酶同功酶ＭＢ（ＣＫ－ＭＢ）峰值，复杂室性期前收缩、泵功能障碍发生率与近期死亡率等均显著低于无心肌缺血预适应老年ＡＭＩ患者（Ｐ＜０．０１与Ｐ＜０．０５）。结论心肌缺血预适应有缩小老年心肌梗塞面积的作用，故对其近期预后可产生有益的影响。     

丝裂素活化蛋白激酶参与缺血预适应的延迟保护作用

为探讨丝裂素活化蛋白激酶参与心肌缺血预适应的延迟保护作用，我们在原位兔心脏缺血预适应和增减乳兔心肌的模型上，检测预适应后即刻、１２小时和２４小时ＭＡＰＫ活性变化，观察预适应后２４小时对再次长时间缺血／再灌注或缺氧／复氧损伤的保护作用（心肌梗塞范围、细胞存活率、ＬＤＨ释放和细胞ＭＤＡ含量），以及用特异的ＭＡＰＫ系统抑制剂ＰＤ０９８０５９抑制预适应后ＭＡＰＫ生的增主对预适应后延迟保护作用的影响。结果提     

心肌缺血预适应对初发急性心肌梗死病人临床及预后的影响

目的探讨心肌缺血预适应对初发急性心肌梗死（AMI）病人梗死范围及近期预后的影响。方法对116例初发AMI骗人．按梗死前48h有无心绞痛分为缺血预适应组（IPC，64例）、无缺血预适应组（NIPC，52例），对比分析两组病人的临床资料。结果IPC组比NIPC组的心肌梗死范围小（P〈0．05），血清心肌酶学峰值低（P〈0．05），恶性心律失常、心力衰竭、心源性休克、室壁瘤发生率及病死率均明显降低（P〈0．05）。结论心肌缺血预适应具有保护心肌、缩小梗死范围。改善近期预后的作用。     

温阳通脉方预处理对心肌缺血再灌注大鼠MDA及SOD的影响

目的 观察温阳通脉方预处理对大鼠心肌缺血再灌注损伤（IR）模型丙二醛（MDA）、超氧化物歧化酶（SOD）含量的影响，探讨温阳通脉方对大鼠再灌注心肌的保护机制。方法 采用结扎大鼠冠状动脉左前降支，缺血30min，再灌注120min的方法建立心肌缺血再灌注损伤模型；缺血5min，再灌注5min，反复3次后缺血30min，再灌注120min建立心肌缺血预适应（IP）模型。检测大鼠灌胃14d后温阳通脉方组、心肌缺血预适应组（IP组）、再灌注损伤纽（IR组）、假性处理组血清MDA、SOD含量。结果 温阳通脉方组、IP组MDA含量低于IR组，SOD高于IR组，差异有统计学意义（P〈0．05）。结论 温阳通脉方预处理后，能降低大鼠心肌缺血再灌注损伤模型MDA含量，升高SOD含量，减轻大鼠急性心肌缺血所致心肌损伤，其机制可能是通过模拟心肌缺血预适应参与心肌保护作用。     

降钙素基因相关肽预适应对在体大鼠心肌缺血/再灌注损伤的保护作用

为探讨降钙素基因相关肽预适应对在体大鼠心肌缺血／再灌注损伤模型是否具有保护作用，用36只SD大鼠随机分为三组：对照组、缺血预适应组和降钙素基因相关肽组。后组持续缺血前20min静脉注射降钙素基因相关肽（10μg／kg）。所有动物均接受30min缺血／2h再灌注。预适应方案由3次5min缺血／再灌注组成。梗塞大小由硝基四唑氮兰染色判定，并以坏死区占危险区的百分数表示。结果发现，缺血预适应和降钙素基因相关肽预适应均能显著地降低缺血和再灌注所致的室性心动过速或心室纤维性颤动的发生。缺血预适应（15．7％，P＜0．01）和降钙素基因相关肽预适应（28．8％，P＜0．01）也均能较对照组（54．0％）显著降低缺血／再灌注后的心肌梗塞面积。本研究结果证实降钙素基因相关肽预适应在在体大鼠模型中也具有心肌保护作用。     

急性心肌梗塞前有无心绞痛对梗塞后心肌损害的影响

目的　探讨心绞痛对急性心肌梗塞（ＡＭＩ）后心肌损害的影响。方法　将８２例急性心肌梗塞患者分成心绞痛组（４８例）和无心绞痛组（３４例）,测定心脏肌酸磷酸激酶（ＣＰＫ）及其同功酶（ＣＫ－ＭＢ）、血清肌钙蛋白（ＣＴｎＴ）、Ｃ反应蛋白（ＣＲＰ）和尿微白蛋白分泌率（ＡＥＲ）变化。结果　心肌梗塞前有心绞痛者的ＣＰＫ、ＣＫ－ＭＢ、ＣＴｎＴ、ＣＲＰ和ＡＥＲ增高水平均较低,与心肌梗塞前无心绞痛患者比较,均有显著性差异（Ｐ＜ ０．０５）。结论　心绞痛对ＡＭＩ的心肌损害有明显保护作用。     

ATP敏感性钾通道在缺血预适应中的作用

缺血预适应对心肌缺血/再灌注损伤有一定的保护作用,而ATP敏感性钾通道（KATP）是缺血预适应的重要环节。KATP开放剂可以产生预适应样心肌保护作用,KATP阻断剂能取消缺血预适应的保护作用。但KATP介导缺血预适应的作用位点是在心肌细胞膜还是在线粒体尚有争议。作者就KATP的结构,功能和在缺血预适应中的作用与机制作一综述。     

冠状动脉造影正常的高血压患者心肌供血分析

目的　为了解冠状动脉造影（ＣＡＧ）正常的高血压患者心肌供血情况。方法选择５２例高血压病Ｉ期或Ⅱ期患者,排除心肌梗塞,心肌病,心瓣膜病等,经ＣＡＧ证实冠状动脉无狭窄者,行心电图、超声心动图、负荷９９ＴＣ－ＭＩＢＩ心肌断层显像检查;３０例ＣＡＧ正常无上述疾病的非高血压患者做对照。结果（１）５２例高血压患者中有２５例（４８．１％）心肌断层显像显示有心肌缺血,对照组缺血者７例（２．３％）,两组差异有显著性;（２）高血压组的室间隔厚度、左房内径明显高于对照组,舒张功能明显低于对照组;（３）高血压病程、心绞痛症状、心电图ＳＴ－Ｔ改变、左室肥厚及舒张功能在高血压缺血组和非缺血组之间差异无显著性。结论高血压患者虽然ＣＡＧ正常,但核素心肌显像仍有心肌缺血存在,考虑为高血压并发微血管病变,导致冠状动脉血流储备能力（ＣＦＲ）下降所致。     

心肌缺血预适应对缩小心肌梗塞范围的临床研究

用培养的兔腹腔巨噬细胞条件培养基作为趋化因子的来源，用改良的Ｂｏｙｄｅｎ小室微孔滤膜法进行单核细胞趋化试验，观察了兔腹腔巨噬细胞条件培养基对单核细胞的趋化作用和抗单核细胞趋化蛋白－１（ｍｏｎｏｃｙｔｅｃｈｅｍｏａｔｔｒａｃｔａｎｔｐｒｏｔｅｉｎ－１，ＭＣＰ－１）抗体对单核细胞迁移的影响。同时用Ｎｏｒｔｈｅｒｎｂｌｏｔ分析方法检测了ＭＣＰ－１ｍＲＮＡ在该巨噬细胞的表达。结果显示，该条件培养基对单核细胞有明显的趋化作用，并被抗ＭＣＰ－１抗体所抑制。同时该巨噬细胞也能表达ＭＣＰ－１ｍＲＮＡ。这提示，巨噬细胞能分泌ＭＣＰ－１，并招引单核细胞迁入内皮下间隙，从而在动脉粥样硬化的发病过程中发挥重要的作用。     

家兔腹腔巨噬细胞能产生单核细胞趋化蛋白-1

用培养的兔腹有空巨噬细胞条件培养基作为趋化因子的来源，用改良的Ｂｏｙｄｅｎ小室微孔滤膜法进行单核细胞趋化试验，观察了兔腹腔巨噬细胞条件培养基对单核细胞的趋化作用和抗单核细胞趋化蛋白－１抗体对单核细胞迁移的影响，同时用Ｎｏｒｔｈｅｒｎ ｂｌｏｔ分析方法检测了ＭＣＰ－１ ｍＲＮＡ在该巨噬细胞的表达。结果显示，该条件培养基对单核细胞有明显的趋化作用，并被抗ＭＣＰ－１抗体所抑制，同时该巨噬细胞也能表达ＭＣ     

玉葵清对糖基化终产物诱导的人肾系膜细胞趋化因子表达的影响

目的 探讨玉葵清对糖基化终产物（AGEs）诱导的人肾系膜细胞（HRMC）趋化因子表达及其趋化效应的影响. 方法 糖基化牛血清白蛋白（AGE-BSA）和玉葵清干预HRMC. 结果 AGE-BSA组较BSA组HRMC趋化单核细胞数增加,单核细胞趋化蛋白-1（MCP-1）、Fractalkine（FKN）中和抗体组HRMC趋化单核细胞数较AGE-BSA组减少;玉葵清组MCP-1、Fractalkine基因表达、上清中的蛋白含量和趋化单核细胞较BSA组降低（P＜0.05）. 结论 玉葵清减弱AGE-BSA诱导的HRMC趋化因子表达及其趋化效应,可能改善DN肾脏炎症反应.     

Loss of CCR2 expression and functional response to monocyte chemotactic protein (MCP-1) during the differentiation of human monocytes: role of secreted MCP-1 in the regulation of the chemotactic response.

Human peripheral blood monocytes differentiate into macrophages when cultured in vitro for a few days. In the present study, we investigated the expression of C-C chemokine and CXCR4 receptors in monocytes at different stages of differentiation. Culturing of monocytes for 7 days resulted in a progressive decrease of the mRNA that encodes for CCR2 and CCR3, whereas the expression of mRNA for other chemokine receptors (CCR1, CCR4, CCR5, and CXCR4) was not substantially affected. The loss of CCR2 mRNA expression in 7-day-cultured macrophages was associated with a strong reduction in the receptor expression at the plasma membrane, as well as in the monocyte chemotactic protein (MCP-1) binding, as compared with freshly isolated monocytes. Furthermore, the biologic response to MCP-1, as measured by intracellular calcium ions increase and chemotactic response, was lost in 7-day-cultured macrophages. Differentiation of monocytes into macrophages also resulted in an increased secretion of MCP-1 that, at least in part, was responsible for the downmodulation of its receptor (CCR2). The loss of CCR2 expression and the parallel increase of MCP-1 secretion triggered by differentiation may represent a feedback mechanism in the regulation of the chemotactic response of monocytes/macrophages.     

Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown aetiology characterized by accumulations of lipoproteinaceous material within the alveoli. The alveolar macrophages become increasingly foamy, and are thought to have a role in the pathogenesis of PAP. However, the mechanisms of macrophage recruitment are unclear. In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20 normal control subjects, the following were examined: the monocyte chemotactic activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent assay, and the MCP-1 expression on lavage cells by immunocytochemistry and in situ hybridization. The monocyte chemotactic activity in the BALF of the PAP patients was markedly elevated, and the activity was completely absorbed by treatment with anti-MCP-1. The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100+/-472 pg x mL(-1)), whereas low levels of MCP-1 were detected in the normal control subjects (mean: never smokers 4.8; smokers 10.4 pg x mL(-1)). MCP-1 protein and messenger ribonucleic acid were expressed by macrophages from the PAP patients, and the expression was reduced according to foaming of the cells; there were monocyte-like macrophages with strong expression, small foamy cells with moderate expression, large foamy cells with a faint expression of MCP-1, and ghost cells with no expression. However, the increase of macrophage number in the PAP BALF was relatively small. These data suggest that monocyte chemoattractant protein(-1) expression by alveolar macrophages represents an amplification mechanism for the recruitment of additional macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may impair the macrophage function and the survival, resulting in the lack of a prominent increase in the macrophage number in bronchoalveolar lavage fluid.     

平滑肌细胞源性趋化因子所致单核细胞迁移的钙依赖性研究

本文以培养的兔主动脉平滑肌细胞条件培养基作为趋化因子的来源，用改良的Ｂｏｙｄｅｎ小室微孔滤膜法进行单核细胞的迁移试验，并观察戊脉胺和细胞外Ｃａ２＋对其影响。用Ｆｕｒａ－２检测单核细胞胞液游离钙浓度，并观察上述条件培养基及戊脉胺对其影响。结果表明，该条件培养基对单核细胞有明显趋化作用并被戊脉胺所抑制；它也能明显地升高单核细胞胞液游离钙浓度，并被戊脉胺所抑制。细胞外Ｃａ２＋也能影响单核细胞的迁移。以上结果提示，单核细胞迁移对细胞内、外Ｃａ２＋均有依赖性。     

Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries

Monocyte chemoattractant protein-1 (MCP-1)/monocyte chemotactic and activating factor (MCAF) has been suggested to promote atherogenesis. The effects of in vivo neutralization of MCP-1 in a rat model were examined in an effort to clarify the role of MCP-1 in the development of neointimal hyperplasia. Competitive polymerase chain reaction analysis revealed maximum MCP-1 mRNA expression at 4 hours after carotid arterial injury. Increased immunoreactivities of MCP-1 were also detected at 2 and 8 hours after injury. Either anti-MCP-1 antibody or nonimmunized goat IgG (10 mg/kg) was then administered every 12 hours to rats that had undergone carotid arterial injury. Treatment with 3 consecutive doses of anti-MCP-1 antibody within 24 hours (experiment 1) and every 12 hours for 5 days (experiment 2) significantly inhibited neointimal hyperplasia at day 14, resulting in a 27.8% reduction of the mean intima/media ratio (P<0.05) in experiment 1 and a 43.6% reduction (P<0.01) in experiment 2. This effect was still apparent at day 56 (55.6% inhibition; P<0.05). The number of vascular smooth muscle cells in the neointima at day 4 was significantly reduced by anti-MCP-1 treatment, demonstrating the important role of MCP-1 in early neointimal lesion formation. However, recombinant MCP-1 did not stimulate chemotaxis of vascular smooth muscle cells in an in vitro migration assay. These results suggest that MCP-1 promotes neointimal hyperplasia in early neointimal lesion formation and that neutralization of MCP-1 before, and immediately after, arterial injury may be effective in preventing restenosis after angioplasty. Further studies are needed to clarify the mechanism underlying the promotion of neointimal hyperplasia by MCP-1.     

Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.

After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of [35S]methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that (i) SMCF is in fact MCP-1 and (ii) MCP-1 is induced by MM-LDL.     

单核细胞趋化蛋白-1在骨髓间质干细胞归巢到大鼠急性梗死心肌中的作用

目的探讨单核细胞趋化蛋白-1(MCP-1)在骨髓间质干细胞(MSCs)归巢到急性梗死心肌中的作用。方法129只大鼠随机分为检测组(65只)和处理组(64只),检测组分为心肌梗死组(35只)和非心肌梗死组(30只),处理组则分为Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组4个亚组(各16只)。检测组以免疫组织化学检测MCP-1在2个亚组大鼠心肌中表达的差异。处理组大鼠心肌梗死4天后予以MCP-1、抗MCP-1抗体干预,同时经尾静脉注射BrdU标记的MSCs,7天后检测心肌梗死区MSCs归巢量,28天后检测大鼠心功能状况、心肌梗死区及其周围的血管密度。结果MCP-1于心肌梗死后第1天即升高,第7天到达峰值,28天时恢复至正常水平。心肌梗死组MSCs归巢量大于非心肌梗死组(P=0.000)。Ⅰ组大鼠心肌梗死区MSCs归巢量、心功能水平及血管密度大于Ⅲ组及Ⅱ组(P<0.01)。结论大鼠心肌梗死后早期梗死区MCP-1表达水平升高;MCP-1能够促进MSCs归巢并改善心功能。     

Membrane type 1-matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium

Membrane type 1-matrix metalloproteinase (MT1-MMP) is involved in endothelial and tumor-cell migration, but its putative role in leukocyte migration has not been characterized yet. Here, we demonstrate that anti-MT1-MMP monoclonal antibody (mAb) impaired monocyte chemotactic protein-1 (MCP-1)-stimulated monocyte migration on fibronectin (FN), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, monocyte transmigration through tumor necrosis factor-alpha (TNF-alpha)-activated endothelium is also inhibited by anti-MT1-MMP mAb. Therefore, regulation of MT1-MMP in human peripheral blood monocytes was investigated. First, MT1-MMP clustering was observed at motility-associated membrane protrusions of MCP-1-stimulated monocytes migrating on FN, VCAM-1, or ICAM-1 and at the leading edge, together with profilin, of monocytes transmigrating through activated endothelial cells. In addition, up-regulation of MT1-MMP expression was induced in human monocytes upon attachment to FN in a manner dependent on alpha4beta1 and alpha5beta1 integrins. Binding of monocytes to TNF-alpha-activated human endothelial cells as well as to VCAM-1 or ICAM-1 also resulted in an increase of MT1-MMP expression. These findings correlated with an enhancement of MT1-MMP fibrinolytic activity in monocytes bound to FN, VCAM-1, or ICAM-1. Our data show that MT1-MMP is required during human monocyte migration and endothelial transmigration and that MT1-MMP localization, expression, and activity are regulated in monocytes upon contact with FN or endothelial ligands, pointing to a key role of MT1-MMP in monocyte recruitment during inflammation.