地塞米松对内毒素作用下人脐静脉内皮细胞表达组织因子、凝血酶调节蛋白和蛋白S的影响

目的观察地塞米松(DEX)对内毒素(LPS)作用于人脐静脉内皮细胞(HUVEC)后表达组织因子(TF)、凝血酶调节蛋白(TM)和蛋白S(PS)的影响.方法24孔板培养的第1～5代HUVEC,在含不同浓度LPS和DEX的无血清培养基中培养一定时间后裂解细胞,应用酶联免疫吸附法(ELISA)测定裂解液中的TF、TM和PS含量.结果在LPS刺激下,HUVEC表达TF的量呈剂量依赖性升高,在LPS0.1μg/ml下TF的表达量为对照组的4倍(P＜0.01),同时加入0.5 μg/ml和1.0 μg/ml DEX则可使TF的表达量由128.3±25.7 pg/105细胞分别降至94.9±19.4 pg/105细胞和98.8±7.8 pg/105细胞(P＜0.05);LPS(0.01～10μg/ml)可抑制HUVEC表达TM,在LPS 10 μg/ml下,TM表达量降至对照组的60%(P＜0.05).DEX可拮抗LPS抑制HUVEC表达TM的效应,0.1 μg/ml、0.5 μg/ml和1.0 μg/ml DEX可使LPS(10 μg/ml)作用下TM的表达量由0.282±0.014 ng/105细胞分别增至0.409±0.009、0.462±0.017和0.362±0.019 ng/105细胞(P＜0.05);LPS(0～10 μg/ml)可抑制HUVEC表达PS,在LPS浓度1.0 μg/ml及10 μg/ml时,PS的表达量分别为对照组的43%和38%(P＜0.01).DEX则拮抗LPS抑制HUVEC表达PS的效应,0.5 μg/ml DEX可使LPS刺激下PS的表达量由13.1±4.8%/2×105细胞增至48.5±10.2%/2×105细胞(P＜0.01).结论LPS促进HUVEC表达TF,抑制HUVEC表达TM和PS.DEX能部分拮抗上述作用,提示DEX可能纠正内毒素血症时的高凝状态.     

Thrombomodulin serum levels in ventilated preterm babies with respiratory distress syndrome

A soluble form of thrombomodulin (TM), an anticoagulant proteoglycan of the endothelial cell membrane, considered a marker of vascular endothelial damage, was measured in plasma of preterm infants with respiratory distress syndrome (RDS). In these patients, lung immaturity leads to endothelial leak of plasma proteins and to surfactant inhibition. In 18 babies with RDS, plasma TM concentration was significantly elevated compared with values of a matched group of babies without pulmonary disease (276.1 ng/ml vs 141.3 ng/ml) (P<0.05). Furthermore, TM levels of mechanical ventilated babies (IPPV) with severe RDS were higher than those of babies with moderate RDS and treated with nasal CPAP (340.9 ng/ml vs 174.2 ng/ml) (P<0.05). Conclusion These data show that TM can be used as marker of pulmonary endothelial damage in preterm babies treated with mechanical ventilation for RDS and suggest early intervention with exogenous surfactant to limit alveolar protein leakage and surfactant inactivation. Received: 20 February 1997 and in revised form: 7 July 1997 / Accepted: 8 July 1997     

Clinical utility of selected disease activity markers in patients with systemic lupus erythematosus

The objective of this study was to assess the utility of measurement of thrombomodulin, antinucleosome antibodies, sVCAM-1, sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R in patients with systemic lupus erythematosus (SLE) and to compare them with traditional markers of SLE activity (anti-dsDNA antibodies, C3, C4) and the ECLAM index of disease activity. The measurement was performed over a 6-month period at three consecutive time points after 3 months in each of the 52 patients with SLE. Anti-dsDNA antibodies, thrombomodulin, antinucleosome antibodies, sVCAM-1m sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R were tested by ELISA technique, while C3, C4 components of complement were tested by nephelometry. Fas ligand and IL-10 did not correlate with the ECLAM index. The rest of the markers showed significant correlation with the disease activity index. Thrombomodulin and anti-dsDNA antibodies reflect in the best way the changing trend in disease activity. Antinucleosome antibodies seem to be a promising marker useful in early diagnosis. Soluble VCAM-1, sICAM-1, neopterin and sIL-2R are interesting molecules with a role in disease pathogenesis, but their practical utility is limited. Received: 27 September 2000 / Accepted: 31 March 2001     

Brenner Tumor of the Ovary: A Comparative Immunohistochemical and Ultrastructural Study With Transitional Cell Carcinoma of the Bladder

Because of a fancied light microscopic resemblance to transitional epithelium (urothelium), Brenner tumor (BT) of the ovary is commonly described as a transitional cell neoplasm. An inability to detect a great deal of similarity between the two at the ultrastructural level prompted this electron microscopic study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To complement the ultrastructural observations, the immunophenotype of 8 benign BTs was evaluated together with that of 12 TCCs of the bladder using antibodies to thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen (CEA), all of which havebeen shown to react with TCCs of urothelial origin. At the ultrastructural level, there was only limited evidence of a morphologic likeness between the epithelial cells of BTs and those of the benign or neoplastic urothelium. The immunophenotype of the two tumors also differed significantly in that there was no reactivity for TM or cytokeratin 20 in the BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were positive for cytokeratin 7 and may express CEA.     

急性冠状动脉综合征患者血清血栓调节蛋白和脂蛋白相关磷脂酶A2水平变化及临床意义

目的:检测急性冠状动脉综合征(ACS)患者血清血栓调节蛋白(TM)及脂蛋白相关磷脂酶A2(Lp-PLA2)水平变化及临床意义。方法:入选冠心病患者120例,分为ACS组69例和稳定性心绞痛(SAP)组51例。再将120例冠心病患者按病变血管支数分为单支病变组(45例)、双支病变组(38例)和3支病变组(37例)。采用Gensini评分系统评定冠状动脉血管病变狭窄程度,按Gensini积分分为轻度病变组(<26分)36例、中度病变组(26~54分)48例和重度病变组(>54分)36例。另选同期有胸痛症状CTA正常的患者20例为对照组。用酶联免疫吸附试验(ELISA)法分别检测血清TM、Lp-PLA2水平。结果:与对照组比较,SAP组、ACS组血清TM、Lp-PLA2水平均明显升高;与SAP组比较,ACS组血清TM、Lp-PLA2均明显升高。单支病变组、双支病变组及3支病变组血清TM、Lp-PLA2均差异无统计学意义。重度病变组血清TM水平明显高于中度病变组和轻度病变组(均P<0.05)。轻度病变组、中度病变组和重度病变组血清Lp-PLA2均差异无统计学意义(P>0.05)。ACS组患者血清TM和Lp-PLA2间呈正相关,而SAP组和对照组间无相关。结论:ACS患者血清TM和Lp-PLA2均升高,说明炎性反应及内皮功能损伤参与了ACS的发病过程,并且两者可能有协同作用。     

血栓调节蛋白和基质金属蛋白酶在脓毒症及多器官功能障碍综合征中的意义

目的检测脓毒症患者血浆血栓调节蛋白(TM)和基质金属蛋白酶9(MMP9)水平,探讨它们对多器官功能障碍综合征(MODS)早期诊断和预后判断的意义。方法采用酶联免疫吸附测定法(ELISA)连续监测32例ICU中脓毒症患者血浆TM和MMP9浓度的动态变化,并选择15例同期健康体检者作为对照。结果与对照组比较,所有患者的血浆TM及MMP9均呈不同程度的升高(P<0.01)。发生MODS患者的TM、MMP9水平比非MODS患者明显升高(P<0.05或P<0.01)。在MODS患者中,非生存组比生存组TM、MMP9升高更明显且持续时间更长(P<0.01)。结论内皮细胞及其细胞外基质的损伤在脓毒症MODS的病理过程中起着重要的作用。TM和MMP9联合应用有助于MODS的早期诊断及其预后的判断。     

血栓调节蛋白水平与结肠直肠癌预后的关系

目的检测结肠直肠癌病人血浆和结肠直肠癌组织中血栓调节蛋白(thrombomodulin,TM)的含量,探讨TM与结肠直肠癌临床病理特征的关系。方法用酶联免疫吸附夹心法检测62例结肠直肠癌病人手术前后的血浆TM水平;免疫组织化学(SP)法检测结肠直肠癌组织、正常肠管组织中的TM蛋白表达水平。结果术前结肠直肠癌组血浆TM水平(8.26±1.36)ng/ml明显高于术后(4.86±0.60)ng/ml和正常对照组(P<0.05);结肠直肠癌组织中TM蛋白表达阳性的病人术前血浆TM水平明显高于结肠直肠癌组织中TM表达阴性者(P<0.05);结肠直肠癌组织中TM蛋白表达阴性的病人手术前后血浆TM水平则无显著性差异(P>0.05);癌组织中TM的阳性表达明显高于癌旁组织以及远端正常肠管组织;TM的表达与临床分期有关(P<0.05),与组织学分级、肌层浸润程度及病人年龄无明显关系(P>0.05)。结论TM表达水平与结肠直肠癌的转移有关,有望成为判断结肠直肠癌病人病情发展和预后的一项新指标。     

血液学指标对复发脑梗死的诊疗价值

目的探讨血液学指标对预测脑梗死复发的价值,为缺血性脑血管病的二级预防开辟新的思路。方法将200例急性脑梗死患者根据头颅MRI结果分为首发性脑梗死组（FIS）109例,复发性脑梗死组（RIS）91例。记录其复发的危险因素,如年龄、吸烟、高血压、糖尿病、高脂血症等,同时于发病72h内测定d-二聚体、蛋白S、蛋白C、抗凝血酶Ⅲ、血栓调节蛋白（TM）、组织型纤溶酶原激活物（t—PA）、组织型纤溶酶原激活物抑制物、同型半胱氨酸（Hcy）以及抗心磷脂抗体等9项血液学指标。结果①RIS组患者平均年龄为（59±9）岁,FIS组患者为（56±10）岁;RIS组患者合并高血压的比率（83．5％）明显高于FIS组（71．6％）。②与FIS组患者相比,RIS组患者血液学指标紊乱严重,9项中有6项表现出明显的差异：蛋白s在RIS和FIS组分别为（23±7）μg/ml、（25±6）μg/ml,P=0．002;蛋白C在RIS和FIS组分别为（4．5±1．5）μg/ml、（4．9±1．7）μg/ml,P=0．05,显示蛋白S和蛋白C在RIS组降低。RIS组TM增高[（30±13）μg/L、（26±7）μg/L,P=0．01];RIS组t—PA较FIS组增多[（7．6±3．0）斗μg/L、（6．7±2．6）μg/L,P=0．025]。RIS组患者血浆Hcy浓度[（23±10）μmol／L]较FIS组[（17±6）μmol／L]升高,P〈0．01。RIS组患者抗心磷脂抗体IgG（ACAIgG）阳性的比例比FIS组高（18．7％、5．5％,P=0．004）。③多因素Logistic回归分析显示,高血压（OR=2．050;95％CI：1．53～6．53）、高龄（OR=1．025;95％CI：1．00～1．05）、蛋白C降低（OR=0．692;95％CI=0．54～0．88）、高同型半胱氨酸血症（OR=1．074;95％CI：1．03～1．12）以及抗心磷脂抗体IgG阳性（OR=3．426;95％CI：1．19～9．84）是预测脑梗死复发的独立危险因素。结论血液学指标失衡可增加脑梗死复发风险,定期检测血液学相关指标有助于早期预测脑梗死的复发。     

汉族急性脑血管病患者血浆血栓调节蛋白的变化和血栓调节蛋白基因Ala455Val(C1418T)多态性研究

目的 探讨急性脑血管病患者血浆可溶性血栓调节蛋白(soluble thrombomodulin,sTM)含量的变化和血栓调节蛋白基因Ala455Val(C1418T)多态性的分布.方法 在79例汉族急性脑血管病患者(脑出血患者30例,脑梗死患者49例)和30名年龄和性别相匹配的健康对照者中,采用聚合酶链反应限制性酶切片段长度多态性分析技术检测TM Ala455Val(C1418T)多态性,酶联免疫吸附试验检测血浆sTM含量.结果 脑梗死组和脑出血组sIM含量分别为(32.08±6.98)ng/ml和(38.93±6.77)ng/ml,显著高于正常对照组的(9.90±3.09)ng/ml(P均<0.01),而且与高血压、糖尿病、心脏病等高危因素无关;脑出血组和脑梗死组TM 1418C/C基因型频率分别为53.3%和57.1%,高于对照组的40%,但无统计学差异.结论 无论足脑出血还是腑梗死患者,血浆sTM含量均显著高于正常人群;汉族人群中脑出血和脑梗死患者TM 1418C/C基因型频率虽然高于正常人群,但并非脑血管病的易感基因.     

新型布尼亚病毒感染患者凝血功能异常及其临床意义

目的探讨新型布尼亚病毒感染后患者发热伴血小板减少症状(SFTS)发病期和恢复期的凝血和血栓相关指标及其临床意义。方法选择2020年4月12日至8月12日在安徽医科大学第一附属医院收治的新型布尼亚病毒感染后SFTS患者,其中SFTS发病期36例,SFTS恢复期18例,并招募36名健康人作为健康对照组,采集血浆标本。回顾性分析血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原含量(FIB)、血浆凝血酶时间(TT)、抗凝血酶-Ⅲ(AT-Ⅲ)、纤维蛋白降解产物(FDP)、D-二聚体(D-D)、血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制物复合物(PIC)、组织型纤溶酶原激活剂-抑制剂1复合物(t-PAIC)浓度。统计比较3组间上述指标的差异。结果与健康对照组比较,SFTS发病组PT[12.5(12.1,13.6)s比10.8(10.5,11.5)s,P<0.05]较长,但仍在正常参考值范围内(14.0~21.0 s);APTT[49.1(42.0,58.2)s比28.5(26.6,30.4)s,P<0.05]较长;FDP[6.07(2.67,8.64)μg/ml比1.00(0.80,1.87)μg/ml]和D-D[2.27(1.04,2.98)μg/ml比0.30(0.21,0.47)μg/ml]较高(P均<0.001);血浆TAT[16.05(8.05,26.58)ng/ml比3.55(2.60,4.85)ng/ml]和PIC浓度[4.44(2.52,5.54)μg/ml比0.84(0.60,1.35)μg/ml]较高(P均<0.001);TM[(19.41±8.29)TU/ml比(9.33±1.89)TU/ml]和t-PAIC浓度[(37.52±21.10)ng/ml比(7.06±3.37)ng/ml]较高(P均<0.001)。SFTS恢复组患者血浆中TAT浓度为9.10(3.95,18.40)ng/ml,仍高于正常参考范围(<4 ng/ml),PIC浓度低于SFTS发病组[1.91(1.45,2.93)μg/ml比4.44(2.52,5.54)μg/ml,P<0.05],TM和t-PAIC低于SFTS发病组(P均<0.05)。结论SFTS患者发病期机体凝血系统激活,血管内皮受到损伤;恢复期血管内皮损伤情况减轻,但机体依然存在一定程度的凝血系统障碍,提示当体内病毒清除后,仍需继续监测凝血指标。