Background Deep venous thrombosis （DVT） can result in pulmonary embolism, a fatal complication that is due to the dislodgement and movement of a blood clot （thrombus） from a limb into the lungs. Genetic risk facto...Background Deep venous thrombosis （DVT） can result in pulmonary embolism, a fatal complication that is due to the dislodgement and movement of a blood clot （thrombus） from a limb into the lungs. Genetic risk factors related to DVT development include mutations in coagulation proteins, especially the endothelial protein C receptor （EPCR）, a component of the anticoagulation protein C （PC） pathway. The objective of the present study was to analyze the relationship between the 6936A/G polymorphism in the EPCR gene and the occurrence of DVT. Methods This study involved 65 patients with DVT and 71 age- and gender-matched healthy controls. Peripheral blood samples were collected from all subjects. Plasma levels of soluble EPCR （sEPCR） were measured by enzyme-linked immunosorbent assay. Genomic DNA was extracted and EPCR gene product was amplified by a standard PCR reaction. Gene product bands were sequenced to identify EPCR gene polymorphisms. Results In the control group, the level of sEPCR in subjects with 6936AG genotype was significantly higher than that in subjects with 6936AA genotype （（0.97_＋0.32） pg/ml vs. （0.61_＋0.24） pg/ml, P 〈0.01）. Similarly in the DVT group, the level of sEPCR in subjects with the 6936AG were greater than that in subjects with the 6936AA genotype （（0.87_-K）.21） pg/ml vs. （0.50-＋0.18） pg/ml, P 〈0.01）. The sEPCR level in DVT patients was significantly higher than that in healthy controls （（0.68_--K）.32） pg/ml vs. （0.54_--K）.22） pg/ml, P 〈0.05）. The 6936AG genotype frequency in DVT patients was significantly higher than that in healthy controls （P 〈0.05）. In contrast, the 6936AA genotype frequency in DVT patients was lower than that in healthy controls （P 〈0.05）. Subjects carrying 6936AG had an increased risk of thrombosis （OR=2.75, 95% CI： 1.04-7.30, P 〈0.05）. Conclusions EPCR gene 6936A/G polymorphism is associated with increased plasma levels of sEPCR. Subjects carrvinq 6936AG likely have an increa展开更多
目的评估血浆内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)和血栓调节蛋白(thrombomodulin,TM)在人工关节置换术围术期的水平变化。方法 119例(男32例,女87例,年龄57.75±12.04岁)于2015年3~6月间在北京积水潭医...目的评估血浆内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)和血栓调节蛋白(thrombomodulin,TM)在人工关节置换术围术期的水平变化。方法 119例(男32例,女87例,年龄57.75±12.04岁)于2015年3~6月间在北京积水潭医院矫形骨科接受全膝关节置换术和全髋关节置换术的患者,观察其在术前、术后第1天和第3天血浆内皮细胞EPCR和TM的浓度变化。结果 (1)血浆EPCR浓度术后第1天与术前相比减低40.34%,术后第3天与术前相比减低49.45%,术后第3天与术后第1天相比减低15.26%,差异均具有统计学意义(F=5.63,均P<0.05);(2)血浆TM浓度术后第1天与术前相比减低12.77%,术后第3天与术前相比减低40.53%,术后第3天与术后第1天相比减低31.83%,差异均具有统计学意义(F=7.87,均P<0.05)。结论关节置换术后3天内EPCR和TM水平进行性减低。展开更多
目的探讨广西地区健康人群与不同地区、种族人群的内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)基因rs9574 C/G(4678 C/G)位点多态性分布频率的差异。方法通过单碱基延伸的PCR技术及DNA测序法检测130例广西正常体检人...目的探讨广西地区健康人群与不同地区、种族人群的内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)基因rs9574 C/G(4678 C/G)位点多态性分布频率的差异。方法通过单碱基延伸的PCR技术及DNA测序法检测130例广西正常体检人群EPCR基因3'-非编码区rs9574 C/G基因型及等位基因型频率,并对比分析其与中国北京人、非洲人、日本人和欧洲人的基因型及等位基因型频率分布差异。结果广西地区健康人群EPCR基因rs9574 C/G位点存在三种基因型,分布频率分别为CC(39.2%)、CG(46.2%)、GG(14.6%),等位基因频率分别为C(62.3%)、G(37.7%)。rs9574 C/G位点基因型及等位基因型分布频率在男女组间相比差异无统计学意义(P>0.05)。广西人群rs9574 C/G位点基因型分布频率与欧洲人和非洲人相比差异有统计学(P<0.05),而与日本人、中国北京人相比差异无统计学意义(P>0.05);等位基因分布频率与非洲人、欧洲人和日本人相比差异有统计学意义(P<0.05),而与中国北京人相比,差异无统计学意义(P>0.05)。结论广西地区人群EPCR基因3'-非编码区rs9574 C/G位点多态性在不同地区、种族人群间的分布频率存在差异。展开更多
目的研究血红素氧化酶-1 (heme oxygenase-1,HO-1)对脓毒症大鼠肾脏的保护作用机制,观察肾脏内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)表达的变化以及血红素氧合酶-1对其影响。方法盲肠结扎-穿孔(cecal ligation an...目的研究血红素氧化酶-1 (heme oxygenase-1,HO-1)对脓毒症大鼠肾脏的保护作用机制,观察肾脏内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)表达的变化以及血红素氧合酶-1对其影响。方法盲肠结扎-穿孔(cecal ligation and perforation,CLP)法制作脓毒症大鼠模型,72只脓毒症大鼠随机分为对照组、CLP组、HO-1促进剂(CLP+hemin)组、HO-1抑制剂(CLP+ZnPP)组,每组18只,后3组大鼠分别于腹腔内注射磷酸盐缓冲液、hemin和ZnPP,12 h后在大鼠腹白线做正中切口约1.5cm,分离盲肠,在盲肠的近端和末端各穿一个孔,挤出少许粪便于腹腔内,回纳盲肠,分层缝合腹腔,造成腹腔感染脓毒症模型。分时相处死大鼠,留取血浆、肾脏组织,分析各组之间肌酐(Cr)、胱抑素C(Cys-C)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)的差别,ELISA法检测血浆EPCR、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)水平变化,肾脏组织经马休黄/猩红/天青石蓝染色法(MSB)对比各组之间病理变化,并应用Western Blot分析肾脏组织EPCR表达水平。结果与对照组相比在脓毒症组中大鼠肾脏微血栓形成明显,凝血功能障碍,炎症反应明显,肾脏功能受损;在HO-1促进剂组中大鼠肾脏微血栓及炎症反应较脓毒症组显著减轻(P<0. 05),肾脏功能得到改善,EPCR表达较脓毒症组上调,差异具有统计学意义(P<0.05);而HO-1抑制剂起到了相反的作用。结论血红素氧合酶-1能够增加脓毒症大鼠肾脏内皮细胞蛋白C受体的表达,发挥抗凝血及抗炎作用,从而改善脓毒症大鼠的肾脏功能。展开更多
文摘Background Deep venous thrombosis （DVT） can result in pulmonary embolism, a fatal complication that is due to the dislodgement and movement of a blood clot （thrombus） from a limb into the lungs. Genetic risk factors related to DVT development include mutations in coagulation proteins, especially the endothelial protein C receptor （EPCR）, a component of the anticoagulation protein C （PC） pathway. The objective of the present study was to analyze the relationship between the 6936A/G polymorphism in the EPCR gene and the occurrence of DVT. Methods This study involved 65 patients with DVT and 71 age- and gender-matched healthy controls. Peripheral blood samples were collected from all subjects. Plasma levels of soluble EPCR （sEPCR） were measured by enzyme-linked immunosorbent assay. Genomic DNA was extracted and EPCR gene product was amplified by a standard PCR reaction. Gene product bands were sequenced to identify EPCR gene polymorphisms. Results In the control group, the level of sEPCR in subjects with 6936AG genotype was significantly higher than that in subjects with 6936AA genotype （（0.97_＋0.32） pg/ml vs. （0.61_＋0.24） pg/ml, P 〈0.01）. Similarly in the DVT group, the level of sEPCR in subjects with the 6936AG were greater than that in subjects with the 6936AA genotype （（0.87_-K）.21） pg/ml vs. （0.50-＋0.18） pg/ml, P 〈0.01）. The sEPCR level in DVT patients was significantly higher than that in healthy controls （（0.68_--K）.32） pg/ml vs. （0.54_--K）.22） pg/ml, P 〈0.05）. The 6936AG genotype frequency in DVT patients was significantly higher than that in healthy controls （P 〈0.05）. In contrast, the 6936AA genotype frequency in DVT patients was lower than that in healthy controls （P 〈0.05）. Subjects carrying 6936AG had an increased risk of thrombosis （OR=2.75, 95% CI： 1.04-7.30, P 〈0.05）. Conclusions EPCR gene 6936A/G polymorphism is associated with increased plasma levels of sEPCR. Subjects carrvinq 6936AG likely have an increa
文摘目的评估血浆内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)和血栓调节蛋白(thrombomodulin,TM)在人工关节置换术围术期的水平变化。方法 119例(男32例,女87例,年龄57.75±12.04岁)于2015年3~6月间在北京积水潭医院矫形骨科接受全膝关节置换术和全髋关节置换术的患者,观察其在术前、术后第1天和第3天血浆内皮细胞EPCR和TM的浓度变化。结果 (1)血浆EPCR浓度术后第1天与术前相比减低40.34%,术后第3天与术前相比减低49.45%,术后第3天与术后第1天相比减低15.26%,差异均具有统计学意义(F=5.63,均P<0.05);(2)血浆TM浓度术后第1天与术前相比减低12.77%,术后第3天与术前相比减低40.53%,术后第3天与术后第1天相比减低31.83%,差异均具有统计学意义(F=7.87,均P<0.05)。结论关节置换术后3天内EPCR和TM水平进行性减低。
文摘目的研究血红素氧化酶-1 (heme oxygenase-1,HO-1)对脓毒症大鼠肾脏的保护作用机制,观察肾脏内皮细胞蛋白C受体(endothelial cell protein C receptor,EPCR)表达的变化以及血红素氧合酶-1对其影响。方法盲肠结扎-穿孔(cecal ligation and perforation,CLP)法制作脓毒症大鼠模型,72只脓毒症大鼠随机分为对照组、CLP组、HO-1促进剂(CLP+hemin)组、HO-1抑制剂(CLP+ZnPP)组,每组18只,后3组大鼠分别于腹腔内注射磷酸盐缓冲液、hemin和ZnPP,12 h后在大鼠腹白线做正中切口约1.5cm,分离盲肠,在盲肠的近端和末端各穿一个孔,挤出少许粪便于腹腔内,回纳盲肠,分层缝合腹腔,造成腹腔感染脓毒症模型。分时相处死大鼠,留取血浆、肾脏组织,分析各组之间肌酐(Cr)、胱抑素C(Cys-C)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)的差别,ELISA法检测血浆EPCR、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)水平变化,肾脏组织经马休黄/猩红/天青石蓝染色法(MSB)对比各组之间病理变化,并应用Western Blot分析肾脏组织EPCR表达水平。结果与对照组相比在脓毒症组中大鼠肾脏微血栓形成明显,凝血功能障碍,炎症反应明显,肾脏功能受损;在HO-1促进剂组中大鼠肾脏微血栓及炎症反应较脓毒症组显著减轻(P<0. 05),肾脏功能得到改善,EPCR表达较脓毒症组上调,差异具有统计学意义(P<0.05);而HO-1抑制剂起到了相反的作用。结论血红素氧合酶-1能够增加脓毒症大鼠肾脏内皮细胞蛋白C受体的表达,发挥抗凝血及抗炎作用,从而改善脓毒症大鼠的肾脏功能。
