细胞因子在急性心肌梗塞中的作用

为探讨细胞因子在急性心肌梗塞（AMI）中的作用，测定了28例AMI患者血清肿瘤坏死因子α（TNFα）和白细胞介素1β（IL－β）水平，并选择13例不稳定型心绞痛（UA）患者和15例健康人作为对照。结果表明：AMI组血清TNFα水平明显高于UA组及正常组（P＜0．01），UA组血清TNFα水平明显高于正常组（P＜0．01）；血清IL－1β水平在严重的AMI患者（心功能KillipⅢ、Ⅳ级）明显高于正常组（P＜0．01）。提示血清TNFα和IL-1β水平与心肌缺血的严重程度有关。     

急性心肌梗塞患者血清肝细胞生长因子变化的意义

目的:探讨急性心肌梗塞(AMI)患者血清肝细胞生长因子(HGF)水平变化的临床意义。方法:入选58例AMI患者(发病<3h组n=22,3-12h组n=36)于入院即刻采静脉血,测心肌酶谱、高敏感性C-反应蛋白(hs-CRP),同时测定20例性别年龄与之相匹配的健康体检者(对照组)的上述指标。结果:入院时AMI组的血清HGF浓度(1635.8±327.0)pg/ml,较正常对照组的(721.8±67.9)pg/ml明显增高(P<0.001),AMI发病3h内血清HGF水平就比正常对照组显著升高(917.6±73.6)pg/mlvs.(721.8±67.9)pg/ml(P<0.001)。AMI患者血清HGF浓度与hs-CRP呈显著正相关(r=0.45,P<0.001)。结论:AMI患者血清HGF浓度升高,可能与AMI的炎症反应有关;有望成为诊断早期AMI的一个新指标。     

Circulating tumour necrosis factor-alpha (cachectin) in myocardial infarction

In a prospective study, 22 patients with prolonged chest pain were monitored by serial serum tumour necrosis factor-alpha (TNF; cachectin) measurements. In five patients serum TNF markedly increased, peaking at greater than 145 ng l-1; all these patients had large infarcts complicated by hypotension, pulmonary oedema and/or arrhythmia. Two of these patients died. In contrast, TNF levels were either normal or only slightly raised in patients with small or uncomplicated infarcts and in patients with prolonged angina without evidence of infarction. The results show that extensive myocardial infarction induces the release of the monocyte/macrophage-derived polypeptide hormone TNF into circulation. This finding may be clinically relevant with respect to systemic metabolic consequences of myocardial infarction.     

脑梗塞合并急性心肌梗死患者危险因素聚集情况分析

自1999年2月以来,我院共收治脑梗塞合并急性心肌梗死患者43例,现分析如下。     

Neutrophil-mediated cartilage injury in vitro is enhanced by tumour necrosis factor alpha

Summary Neutrophil functions relevant to tissue damage are altered by cytokines such as tumour necrosis factor alpha (cachectin, TNF), known to be present in inflammatory foci. In this study we examined the effect of TNF on neutrophil-mediated cartilage damage in vitro. Human neutrophils were able to injure both human and bovine articular cartilage slices by degrading proteoglycan and inhibiting its synthesis. Recombinant human TNF enhanced neutrophil-mediated degradation of proteoglycan, even when neutrophils were preincubated with TNF and washed before incubating with cartilage. TNF alone degraded proteoglycan and inhibited its synthesis. Neutrophil-mediated inhibition of proteoglycan biosynthesis was increased after incubating cartilage together with neutrophils and TNF, but was unaltered when neutrophils were preincubated with TNF. We conclude that TNF enhances neutrophil injury to articular cartilage.     

急性心肌梗死再通治疗后体内细胞因子活性变化

目的 :了解临床心肌缺血 -再灌注过程与细胞因子间的关系。方法 :将 1 6例急性心肌梗死患者依冠状动脉是否再通分为两组 ,分别连续测定白细胞介素 - 1、白细胞介素 - 6及肿瘤坏死因子活性。结果 :溶栓后 1 2～ 48h三种细胞因子活性再通组均明显高于未通组。结论 :细胞因子活性升高与心肌缺血 -再灌注过程明显相关。     

Comparative analysis of the genetic associations of HLA-DR3 and tumour necrosis factor alpha with human IDDM

Summary Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ alleles, but a pathogenic role for TNF-α in the class III region of the MHC has also been implied. We therefore tested whether there was any independent association between a biallelic TNF polymorphism and IDDM. The TNF2 allele was present in 61 of 114 (54 %) IDDM patients compared to 101 of 253 (40 %) control subjects (odds ratio 1.73; p<0.02). Stratification analysis in individuals matched for HLA-DR3 revealed, however, that this association was not independent of HLA-DR3 and is most likely to be a result of linkage disequilibrium between these alleles. [Diabetologia (1994) 37: 500–503] Received: 29 June 1993 and in final revised form: 29 November 1993     

Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6.

Transcobalamin (TCII) and haptocorrins (TCI and III), tumour necrosis factor alpha (TNF), interleukin-6 (IL6) and parameters of disease activity were assessed in 20 rheumatoid arthritis (RA) patients without anaemia and 19 subjects with anaemia of chronic disease (ACD) in order to determine if there was a possible correlation between these parameters. TCII, TNF and IL6 correlated positively with RA disease activity parameters, whereas their serum levels were higher in the ACD patients. TC levels were not correlated with cytokine levels. Vitamin B12 serum levels were lower in ACD. We conclude that in RA, elevated serum TCII levels are possibly mediated by increased RA disease activity, but probably not by actions of TNF or IL6. Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels. However, these preliminary findings require further confirmation.     

高剂量极化液对心肌梗死患者细胞凋亡因子的影响

目的探讨急性心肌梗死(AMI)再灌注治疗联合高剂量极化液(GIK)持续静脉滴注对心肌损伤和细胞凋亡因子sFas和sFasL血清水平的影响。方法74例AMI患者再灌注后随机分为GIK组(35例)和非GIK组(39例),另设正常对照组(34例)。GIK组在接受再灌注后即刻予以高剂量GIK滴注24h。检测患者入组即刻、24h、3d、7d和14d血清sFas和sFasL水平。结果(1)AMI患者入组即刻血清sFas和sFasL水平明显高于正常对照组(P<0.01);(2)再灌注后GIK组和非GIK组血清sFas水平在24h显著降低(P<0.01),3～7d再次增高(P<0.01);(3)最为重要的发现是在14d时,sFas水平在GIK组明显降低(P<0.01),而非GIK组14d与7d比较差异无统计学意义;(4)血清sFasL水平在14d期间GIK组与非GIK组比较差异无统计学意义(P>0.05)。结论再灌注治疗联合高剂量GIK滴注明显降低AMI患者血清sFas水平,提示高剂量GIK可能通过减少缺血再灌注损伤实现对缺血心肌的保护作用。     

Interleukin‐10 and tumour necrosis factor‐alpha serum levels in chronic Chagas disease patients

In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin‐10 and tumour necrosis factor‐alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin‐10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor‐alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow‐up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.     

Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells

Tumour necrosis factor (TNF)-α exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro , including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-α-driven growth regulation of AML blasts in vitro . Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-α-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-α-induced autocrine growth. In contrast, the TNF-α-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-α on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-α-signalled growth inhibition is exclusively transduced via TNF-Rp55.     

Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia

Genetic polymorphisms in the tumour necrosis factor (TNF) locus influence the outcome of non-Hodgkin's lymphoma (NHL). We investigated whether these polymorphisms might contribute to the clinical course of childhood acute lymphoblastic leukaemia (ALL). Genomic DNA from 214 childhood ALL patients was analysed. Patients with a high-risk haplotype were older than patients with low-risk haplotype (P = 0.024). No statistically significant associations were found between TNF haplotype and sex, WBC counts, central nervous system involvement, immunophenotype, response to chemotherapy, and event-free survival. These data suggest that genetic polymorphisms in the TNF locus have a limited effect on the outcome of childhood ALL.     

急性心肌梗死再灌注心律失常不增加心肌损伤

目的探讨急性心肌梗死（AMI）患者PCI再灌注心律失常的临床意义。方法回顾性分析近年在我院接受直接PCI且成功开通梗死相关血管（IRA）的AMI患者228例。将其中开通IRA后数分钟内发生心肌缺血再灌注损伤（MIRI）的119例患者（MIRI组）分为3个亚组,即严重心动过缓和低血压（缓慢性心律失常组）、需电复律的严重室性心律失常（快速性心律失常组）和IRA前向血流≤TIMI2级且除外急性闭塞（无复流组）。结果（1）临床和造影资料：与无MIRI组相比,MIRI组缺血时间短,梗死前心绞痛所占比例低,多支血管病变、下壁梗死、右冠状动脉IRA、PCI前IRA血流TIM10级和肾功能不全所占比例高,住院病死率较高（13．4％比4．6％,P=0．021）。（2）血清心肌酶水平：缓慢性心律失常组肌酸激酶（OK）峰值中位数显著低于无MIRI组（20LOIU／L比2521IU／L,P=0．039）,肌酸激酶同工酶（CK．MB）峰值中位数有低于无MIRI组的趋势（98IU／L比142IU／L,P=0．091）;快速性心律失常组CK峰值中位数（2317IU／L）和CK-MB峰值中位数（134IU／L）与无MIRI组相比差异无统计学意义（P=0．627,0．500）;无复流组CK峰值中位数（4573IU／L）和CK-MB峰值中位数（338IU／L）均显著高于无MIRI组（P均=0．000）。（3）超声心功能：无复流组左心室射血分数显著低于无MIRI组（38．7％±8．3％比51．2％±8．1％,P=0．000）,左心室舒张末期容积显著大于快速性心律失常组[（135±32）ml比（105±19）ml,P=0．029],左心室收缩末期容积显著大于无MIRI组[（82±33）ml比（54±24）ml,P=0．008]和缓慢性心律失常组[（56±19）ml,P=0．025]。结论再灌注心律失常可能提示梗死区存活心肌多,而且不增加心肌损伤;无复流增加心肌损伤,导致永久的心功能障碍。     

经静脉心肌声学造影评价心肌梗死后存活心肌的价值

目的　探讨经静脉心肌声学造影 (MCE)对心肌梗死后存活心肌的诊断价值。方法　 2 4例心肌梗死患者用二维超声评价室壁运动情况 ,同时经静脉进行MCE ,以 3个月后静态超声心动图左室心肌节段性运动改善为依据评价MCE对心肌梗死后存活心肌的诊断价值。结果　在 2 4例病人的 384个心肌节段中 ,运动异常节段 184个。在运动异常的 184个节段中 ,MCE1分 39段 ,0 5分 5 0段 ,0分 95段。 3个月复查 79个节段有运动改善 ,其中 39段来自MCE1分的心肌 ,4 0段来自MCE0 5分的心肌。MCE对预测心肌梗死后室壁运动改善的敏感性、特异性、阳性预测值、阴性预测值及准确率分别为 :10 0 %、89 7%、84 8%、10 0 %和 94 6 %。结论　MCE能比较准确地预测心肌梗死后心肌的存活性     

粒细胞-巨噬细胞集落刺激因子对大鼠急性心肌损伤血管新生的作用

目的 观察粒细胞-巨噬细胞集落刺激因子(GM-CSF)预处理对异丙肾上腺素(Iso)所致大鼠急性心肌损伤后新生血管密度的影响.方法 雄性、成年Wistar大鼠60只,体质量约190 g.按体质量将大鼠随机分成3组:对照组,GM-CSF预处理组(GM-CSF组),Iso损伤组,每组20只.GM-CSF组提前给予注射用人重组(rh)GM-CSF 5.0μg/kg,1次/d,尾静脉注射,连续3 d.在注射后的第3天,GM-CSF组和Iso损伤组同时给予Iso,按15.0 mg/kg腹腔注射,1次/d,连续3 d;对照组给予等量次生理盐水.注射后第10天.观察各组大鼠心肌损伤的病理改变和坏死灶面积;免疫组化方法测量、等大鼠心肌组织中新生血管密度指数:RT-PCR法检测大鼠心肌组织中多肽抗原(CD34)、血管内皮生长因子(VEGF)及VEGF受体(KDR/flk-1)的表达.结果 大鼠心肌坏死面积组问比较差异有统计学意义(F=10.07,P<0.01),其中GM-CSF组[(37.37 ±12.98)%]明显少于Iso损伤组[(45.51±14.96)%,P<0.05].大鼠心肌组织中新生血管密度指数组间比较差异有统计学意义(F=25.54,P<0.05),其中GM-CSF组[(3980.05±477.22)个/mm2]显著高于Iso损伤组[(2605.93 ±361.49)个/mm2,P<0.01].大鼠心肌CD34、VEGF、KDR/flk-1 mRNA表达组间比较差异有统计学意义(F值分别为17.83、4.29、4.10,P均<0.01);GM-CSF组[CD34(44.04±10.13).VEGF(49.40±11.59),KDR/flk-1(46.49 ±7.90)]均高于Iso损伤组[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01).P均<0.01].大鼠心肌VEGF mRNA表达与其受体KDR/flk-1 mRNA表达呈正相关(r=0.725,R2=0.526,P<0.01).结论 GM-CSF预处理可增加大鼠心肌中新生血管密度.减轻Iso所致的大鼠心肌损伤.

Abstract：

Objective To study the effect of granulocyte-macrophage colony-stimulating factor(GM-CSF)on angiogenesis of rat with acute myocardial injury induced by isoproterenol(Iso). Methods A total of 60 adult male Wistar rats were randomly divided into 3 groups: normal control group, GM-CSF pretreatment group (GM-CSF group), and lso injury group, 20 rats in each group. GM-CSF group was administered recombinant human(rh)GM-CSF(5.0 μg/kg), through tail intravenous injection once a day for three days. Then the GM-CSF group and the Iso injury group were anesthetized by intraperitoneal injection of lso( 15.0 mg/kg) once a day for three days. The same dose of saline was administered in the same way to the control rats. Ten days after injection, pathological changes of myocardial damage and infarct area were examined by immunohistochemistry. The mRNA expression levels of polypeptide antigen (CD34), vascular endothelial growth factor (VEGF) and its receptor KDR/flk- 1 were measured by RT-PCR. Results The difference of myocardial necrosis area between groups was statistically significant(F=10.07, P < 0.01), in which GM-CSF group[(37.37 ± 12.98)%] was significantly less than Iso injury group[(45.51 ±14.96)%, P < 0.05]. The difference of myocardial neovascularization density index of rats between groups was statistically significant ( F = 25.54, P < 0.05 ), in which GM-CSF group [(3980.05 ± 477.22) No/mm2] was significantly higher than Iso injury group((2605.93±361.49)No/mm2,P<0.01).The differences of myocardial CD34,VEGF,KDR/flk-1 mRNA expression between groups were statistically significant(F=17.83,4.29,4.10,all P<0.01).Compared to Iso mjury group[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01)]were higher in the GM-CSF group[CD34(44.04±10.13),VEGF(49A±11.59),and KDR/flk-1(46A9±7.90),all P<0.01].The expressions of myocardiM VEGF mRNA and its receptor KDR/flk-1 mRNA was positively correlated(r=0.725,R2=0.526,P<0.01).Conclusions GM-CSF prelreatmcnt increases the density ofnew blood vessels in myocardium,and reduces the Iso-induced myocardial injury in rats.     

急性心肌梗死发作期间组织因子途径变化的观察

目的：观察急性心肌梗死（AMI）发作期间组织因子途径的变化。方法：69列临床确诊的AMI患和30例健康中老年人（作对照）被纳入研究对象。血浆中的组织因子（TF）和组织因子途径抑制物（TFPI）的活性测定采用发色底物法,TF和TFPI抗原采用ELISA法。激活的凝血因子Ⅶa采用重组可溶性TF法。凝血因子Ⅶ促凝活性采用活性测定法。结果：与对照组相比,AMI患血浆中TF、TFPI的活性均显增加[分别为5．67（1．77－54．95）mU/ml vs2.36(1.13-6.42)mU/ml,P＜0．01;224．85（86．65－512．12）％vs 138．75（51．72－297．2）％,P＜0．01]。同时TF、TFPI的抗原、凝血因子Ⅶa的活性亦有明显升高,但凝血因子Ⅶ促凝活性无显变化。结论：AMI发作期间体内组织因子途径被启动,血液呈现高凝状态。     

急性心肌梗死血清诊断指标比较

目的 :建立血清磷酸肌酸激酶同工酶 MB(CK- MB)与心肌肌钙蛋白 I(c Tn I)测定的方法 ,并通过与CK、谷草转氨酶 (AST)、乳酸脱氢酶 (L DH)比较阐述其对急性心肌梗死 (AMI)的诊断价值。方法 :共观察急性心肌梗死 (AMI) 6 5例 ,陈旧性心肌梗死 2 8例 ,稳定性心绞痛 17例 ,阵发性室上性心动过速 49例。建立 CK- MB单克隆抗体吸附测定与 c Tn I EL ISA双夹心测定的方法。同时观察血清 CK- MB、c Tn I、CK、AST、L DH在 AMI等疾患中的变化。结果 :血清 CK- MB单克隆抗体吸附法与 c Tn I EL ISA双夹心法回收率分别为 97%～ 113%、94.6 %～ 10 5 .6 % ,标准曲线相关系数分别为 0 .993与 0 .990 ,分别与琼脂糖电泳法及国外实验室检测法对比结果基本一致。 AMI胸痛发生后 12 h内血清 CK- MB的敏感性最高 ,12～ 2 4h的敏感性与 CK、c Tn I相当 ,高于 AST和L DH,而 2 4h后血清 c Tn I的敏感性最高 ;血清 CK- MB与 c Tn I对 AMI诊断的特异性和诊断有效性明显高于CK、AST、L DH。结论 :血清 CK- MB单克隆抗体吸附法与 c Tn I EL ISA双夹心法的敏感性和特异性高 ,CK- MB与c Tn I两个指标相互补充 ,对诊断 AMI有重大的临床价值     

Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells

Tumour necrosis factor (TNF)-α exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-α-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-α-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-α-induced autocrine growth. In contrast, the TNF-α-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-α on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-α-signalled growth inhibition is exclusively transduced via TNF-Rp55.     

老年急性心肌梗死患者肿瘤坏死因子-α和白细胞介素-10的变化及辛伐他汀的干预作用

目的　探讨老年人急性心肌梗死 (AMI)患者外周循环肿瘤坏死因子 α(TNF α)和白细胞介素 10 (IL 10 )的变化及辛伐他汀对TNF α和IL 10的作用。方法　测定 39例老年AMI患者 (AMI组 )、2 0例老年陈旧性心肌梗死 (OMI)患者 (OMI组 )及 2 0例正常老年人 (正常人组 )血清TNF α和IL 10浓度。 39例AMI患者入院后随机分为辛伐他汀组和对照组 ,治疗前、治疗后 1周和 6周测定血清TNF α和IL 10浓度。结果　AMI组TNF α、IL 10水平明显高于OMI组 ;OMI组TNF α水平明显高于正常人组 ;正常人组血清IL 10未检测到。辛伐他汀组和对照组经治疗后 1周、6周TNF α水平均显著下降 ,6周后辛伐他汀组TNF α水平显著低于对照组。辛伐他汀组和对照组IL 10水平 6周后均显著降低 ,但两组差异无显著性意义。结论　辛伐他汀具有降低AMI患者血清TNF α水平的作用 ,对IL 10水平无影响