不同比例输血策略对创伤-失血性休克大鼠的凝血指标、血浆代谢指标影响及作用机制分析

摘要 目的：探讨不同比例输血策略对创伤-失血性休克大鼠的凝血指标、血浆代谢指标影响及作用机制。方法：选择Sprague- Dawley大鼠24只,制备创伤-失血性休克动物模型,采用血气分析仪检测凝血指标（PT及ATPP）血气分析指标（包括pH、PO₂、PCO₂、乳酸）,采用比色法检测常见代谢酶活性,采用PCR法检测mRNA含量,记录并对比目标血压为80 mmHg时B、C、D三组大鼠的输血量。结果：与A组大鼠相比,B、D组大鼠的ATPP、PT水平明显较高(P<0.05),A组与C组间对比无统计学意义(P>0.05);与B组大鼠相比,D组大鼠的ATPP、PT水平明显较低(P<0.05)。与A组相比,B、C、D组大鼠的pH、PO₂水平明显降低、PCO₂及乳酸水平明显升高对比(P>0.05);与B组大鼠相比,C、D组大鼠的pH、PO2明较高,PCO2、乳酸明显较低(P<0.05);C、D组间对比无统计学意义(P>0.05)。四组大鼠的血浆肌酸激酶、天门冬氨酸基转移酶、碱性磷酸酶、丙氨酸氨基转移酶活动水平对比无统计学意义(P>0.05)。与A组相比,B、D组大鼠的血浆miR-24水平明显较高,肝脏FX mRNA水平明显较低(P<0.05),C组大鼠的血浆miR-24与肝脏FX mRNA与A组对比无统计学意义(P>0.05);与B组相比,D组大鼠的血浆miR-24水平明显较低,肝脏FX mRNA水平明显较高(P<0.05)。达到目标血压为80 mmHg时,输血量B组>C组>D组(F=133.139,P<0.001)。结论：新鲜冰冻血浆：红细胞比为1:1的输血策略较1：2.5的输血策略对创伤-失血性休克大鼠的复苏效果更好,可能与其降低大鼠的循环miR-24水平,提高肝脏FX mRNA水平表达有关。     

过敏性紫癜患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化及相关性研究

摘要 目的：探讨过敏性紫癜（HSP）患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化,并分析HSP患者血管内皮功能与凝血功能的相关性。方法：选择2018年2月至2020年2月期间我院收治的HSP患者93例,按照随机数字表法将患者分为对照组（n=46）和观察组（n=47）,其中对照组给予糖皮质激素治疗,观察组给予银杏达莫注射液治疗,对比两组疗效、血管内皮功能、凝血功能的变化及紫癜性肾炎的发生率,并分析HSP患者血管内皮功能与凝血功能的相关性。结果：观察组治疗2周后的总有效率95.74%（45/47）,较对照组的76.09%（35/46）升高（P<0.05）。两组患者治疗2周后血清血管内皮生长因子（VEGF）、内皮素-1（ET-1）水平均降低,且观察组低于对照组（P<0.05）。两组患者治疗2周后纤维蛋白原（FIB）、D-二聚体（D-D）、血小板计数（PLT）均降低,且观察组低于对照组（P<0.05）,凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）均升高,且观察组高于对照组（P<0.05）。两组紫癜性肾炎发生率对比无统计学差异（P>0.05）。观察组患者中VEGF、ET-1均与FIB、D-D、PLT呈正相关,而与PT、APPT、TT呈负相关（P<0.05）。结论：HSP的发病过程中存在血管内皮细胞损伤及血液高凝状态,采用银杏达莫注射液治疗HSP患者,疗效显著,可有效改善患者血管内皮功能、凝血功能,且血管内皮功能与凝血功能存在一定的相关性。     

脓毒症大鼠肝肾功能、凝血功能和炎症指标的变化及意义

摘要 目的：研究脓毒症大鼠肝肾功能、凝血功能和炎症指标的变化及意义。方法：选取SPF级雄性SD大鼠20只,以随机数字表法将其分成实验组与假手术组,每组各10只。其中实验组通过盲肠穿刺结扎制备脓毒症大鼠模型,假手术组大鼠仅翻动盲肠,不作结扎处理。分别采集所有大鼠术后0 h、6 h、12 h、24 h时的尾静脉血3 mL,检测并比较上述时间点两组大鼠的肝肾功能、凝血功能和炎症指标水平的差异。结果：实验组术后6 h、12 h、24 h的谷丙转氨酶（ALT）、尿素氮（BUN）以及肌酐（Cr）水平均高于假手术组（P＜0.05）。实验组术后24 h的活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、纤维蛋白原（FIB）水平均高于假手术组（P＜0.05）。实验组大鼠术后6 h、12 h、24 h的血清白细胞计数（WBC）、白细胞介素-6（IL-6）、降钙素原（PCT）水平均高于假手术组（P＜0.05）。结论：脓毒症大鼠肝肾功能存在明显的受损,凝血功能障碍明显,且机体内会释放大量的炎症因子。     

Multiple Ligands of von Willebrand Factor-binding Protein (vWbp) Promote Staphylococcus aureus Clot Formation in Human Plasma

Staphylococcus aureus secretes coagulase (Coa) and von Willebrand factor-binding protein (vWbp) to activate host prothrombin and form fibrin cables, thereby promoting the establishment of infectious lesions. The D1-D2 domains of Coa and vWbp associate with, and non-proteolytically activate prothrombin. Moreover, Coa encompasses C-terminal tandem repeats for binding to fibrinogen, whereas vWbp has been reported to associate with von Willebrand factor and fibrinogen. Here we used affinity chromatography with non-catalytic Coa and vWbp to identify the ligands for these virulence factors in human plasma. vWbp bound to prothrombin, fibrinogen, fibronectin, and factor XIII, whereas Coa co-purified with prothrombin and fibrinogen. vWbp association with fibrinogen and factor XIII, but not fibronectin, required prothrombin and triggered the non-proteolytic activation of FXIII in vitro. Staphylococcus aureus coagulation of human plasma was associated with the recruitment of prothrombin, FXIII, and fibronectin as well as the formation of cross-linked fibrin. FXIII activity in staphylococcal clots could be attributed to thrombin-dependent proteolytic activation as well as vWbp-mediated non-proteolytic activation of FXIII zymogen.     

Batroxobin Binds Fibrin with Higher Affinity and Promotes Clot Expansion to a Greater Extent than Thrombin

Batroxobin is a thrombin-like serine protease from the venom of Bothrops atrox moojeni that clots fibrinogen. In contrast to thrombin, which releases fibrinopeptide A and B from the NH₂-terminal domains of the Aα- and Bβ-chains of fibrinogen, respectively, batroxobin only releases fibrinopeptide A. Because the mechanism responsible for these differences is unknown, we compared the interactions of batroxobin and thrombin with the predominant γ_A/γ_A isoform of fibrin(ogen) and the γ_A/γ′ variant with an extended γ-chain. Thrombin binds to the γ′-chain and forms a higher affinity interaction with γ_A/γ′-fibrin(ogen) than γ_A/γ_A-fibrin(ogen). In contrast, batroxobin binds both fibrin(ogen) isoforms with similar high affinity (K_d values of about 0.5 μm) even though it does not interact with the γ′-chain. The batroxobin-binding sites on fibrin(ogen) only partially overlap with those of thrombin because thrombin attenuates, but does not abrogate, the interaction of γ_A/γ_A-fibrinogen with batroxobin. Furthermore, although both thrombin and batroxobin bind to the central E-region of fibrinogen with a K_d value of 2–5 μm, the α(17–51) and Bβ(1–42) regions bind thrombin but not batroxobin. Once bound to fibrin, the capacity of batroxobin to promote fibrin accretion is 18-fold greater than that of thrombin, a finding that may explain the microvascular thrombosis that complicates envenomation by B. atrox moojeni. Therefore, batroxobin binds fibrin(ogen) in a manner distinct from thrombin, which may contribute to its higher affinity interaction, selective fibrinopeptide A release, and prothrombotic properties.     

Ligand Binding to Anion-binding Exosites Regulates Conformational Properties of Thrombin

Thrombin participates in coagulation, anticoagulation, and initiation of platelet activation. To fulfill its diverse roles and maintain hemostasis, this serine protease is regulated via the extended active site region and anion-binding exosites (ABEs) I and II. For the current project, amide proton hydrogen-deuterium exchange coupled with MALDI-TOF mass spectrometry was used to characterize ligand binding to individual exosites and to investigate the presence of exosite-active site and exosite-exosite interactions. PAR3(44–56) and PAR1(49–62) were observed to bind to thrombin ABE I and then to exhibit long range effects over to ABE II. By contrast, Hirudin(54–65) focused more on ABE I and did not transmit influences over to ABE II. Although these three ligands were each directed to ABE I, they did not promote the same conformational consequences. d-Phe-Pro-Arg-chloromethyl ketone inhibition at the thrombin active site led to further local and long range consequences to thrombin-ABE I ligand complexes with the autolysis loop often most affected. When Hirudin(54–65) was bound to ABE I, it was still possible to bind GpIbα(269–286) or fibrinogen γ′(410–427) to ABE II. Each ligand exerted its predominant influences on thrombin and also allowed interexosite communication. The results obtained support the proposal that thrombin is a highly dynamic protein. The transmission of ligand-specific local and long range conformational events is proposed to help regulate this multifunctional enzyme.     

凝血功能对胸腔镜手术治疗非小细胞肺癌疗效评估及预后预测的临床价值分析

目的:探究凝血功能对胸腔镜手术治疗非小细胞肺癌的疗效评估及预后预测的临床应用价值。方法:选择在我院行胸腔镜手术治疗的50例非小细胞肺癌患者为研究对象,分析凝血功能指标与患者临床病理特征的关系,比较患者治疗前后凝血功能指标水平的变化,并对患者的预后进行预测。结果:不同性别、病理类型、病理期及淋巴结转移状态患者的凝血功能指标比较差异具有统计学意义(P0.05);患者行胸腔镜手术治疗后凝血功能指标水平变化显著(P0.05);Log-Rank单因素生存分析显示凝血功能指标中纤维蛋白原(Fib)和D-二聚体(D-D)水平高于平均值的非小细胞肺癌患者生存率显著降低(P0.05);Logistic多因素回归分析显示Fib和D-D升高为影响非小细胞肺癌患者生存期和预后的独立危险因素(P0.05)。结论:凝血功能指标与胸腔镜手术治疗的非小细胞肺癌患者疗效及预后有一定的相关性,Fib和D-D是患者预后的独立危险因素。     

替格瑞洛联合瑞舒伐他汀钙片对冠心病患者心功能、凝血功能及基质金属蛋白酶的影响

目的:探究替格瑞洛联合瑞舒伐他汀钙片及阿司匹林对冠心病患者心功能、凝血功能及基质金属蛋白酶的影响。方法:选择2015年7月～2018年12月于我院心内科接受治疗的77例冠心病患者,按患者是否服用替格瑞洛将其分为替格瑞洛组和对照组。对照组在常规西药治疗方法上服用阿司匹林和瑞舒伐他汀钙片,替格瑞洛组在对照组的治疗方法上联合替格瑞洛。检测和比较两组治疗前及治疗4周后心功能指标[肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白Ⅰ(cTnⅠ)],炎症反应指标[肿瘤坏死因子(TNF-α)、单核细胞趋化蛋白-l(MCP-1)、C反应蛋白(CRP)],凝血功能指标[活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(FIB)]及基质金属蛋白酶9(MMP-9)和基质金属蛋白酶12(MMP-12)水平的变化。结果:治疗4周后,两组患者血清CK-MB、cTnⅠ水平、TNF-α、MCP-1、CRP、MMP-9、MMP-12及FIB水平均显著低于治疗前(P0.05),且替格瑞洛组患者以上指标均显著低于对照组(P0.05);两组APTT、PT、TT均显著高于治疗前,且替格瑞洛组以上指标均明显高于对照组(P0.05)。结论:替格瑞洛联合联合阿司匹林及瑞舒伐他汀钙片可有效改善冠心病患者的心功能和凝血功能,可能与其有效减轻炎症反应及减少基质金属蛋白酶的含量有关。     

阿托伐他汀对慢性硬膜下血肿患者术后MBI、CSS评分的影响

目的:探讨阿托伐他汀对慢性硬膜下血肿(CSDH)患术后改良barthel指数(MBI)和中国卒中量表(CSS)评分的影响。方法:选择2014年2月至2019年2月我院接诊的126例CSDH术后患者进行研究,通过随机数表法将其分为观察组和对照组,每组各63例。两组患者均接受钻孔引流术,对照组术后给予常规处理,观察组联合阿托伐他汀口服治疗,均持续用药1个月。比较两组治疗前后血清神经元特异性烯醇化酶(NSE)、人S100B蛋白(S-100B、肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、MBI、CSS评分的变化情况及不良反应的发生情况和复发情况。结果:观察组治疗后血清NSE、S-100B、CRP、TNF-α、IL-1水平均低于对照组(P0.05),MBI评分高于对照组,CSS评分低于对照组(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05),观察组复发率明显低于对照组(P0.05)。结论:阿托伐他汀能降低CSDH患者患术后炎症反应,提高MBI、CSS评分,降低复发率,且不增加不良反应。     

Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus pyogenes

Recent studies have shown that activation of complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in >100 different serotypes due to sequence variation in the surface-associated M protein. Cases of invasive and life-threatening S. pyogenes infections are commonly associated with isolates of the M1 serotype, and in contrast to the large majority of M serotypes, M1 isolates all secrete the SIC protein. Here, we show that SIC interferes with the activation of the contact system and blocks the activity of antibacterial peptides generated through complement and contact activation. This effect promotes the growth of S. pyogenes in human plasma, and in a mouse model of S. pyogenes sepsis, SIC enhances bacterial dissemination, results which help explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.