rt-PA动脉溶栓联合血管内支架成形术对早期急性脑梗死患者纤溶系统和血清神经功能损伤指标的影响

摘要 目的：探讨重组人组织型纤溶酶原激活物（rt-PA）动脉溶栓联合血管内支架成形术治疗早期急性脑梗死（ACI）的疗效及对纤溶系统和血清神经功能损伤指标的影响。方法：选取我院2018年9月~2021年3月间接收的80例早期ACI患者。根据随机数字表法分为对照组38例（rt-PA动脉溶栓治疗）和研究组42例（rt-PA动脉溶栓联合血管内支架成形术治疗）。对比两组血管再通情况、纤溶系统和血清神经功能损伤指标变化、日常生活能力量表（ADL）及美国国立卫生研究院卒中量表（NIHSS）评分,观察两组预后情况。结果：研究组的血管完全再通率高于对照组（P<0.05）。研究组治疗后1 d、治疗后7 d、治疗后3个月NIHSS评分低于对照组,ADL评分高于对照组（P<0.05）。研究组治疗7 d后血管性假血友病因子（vWF）、血浆纤溶酶原激活物抑制剂-1（PAI-1）低于对照组,组织型纤溶酶原激活剂（tPA）高于对照组（P<0.05）。研究组治疗7 d后胶质纤维酸性蛋白（GFAP）、神经元特异性烯醇化酶（NSE）、S100β蛋白低于对照组（P<0.05）。研究组患者的再发脑梗死率、死亡率低于对照组（P<0.05）。结论：rt-PA动脉溶栓联合血管内支架成形术治疗早期ACI患者,可改善患者近远期疗效和预后,有效调节纤溶系统,减轻机体神经功能损伤,提高患者日常生活能力。     

血清UA、Hcy、LDL-C联合监测对急性脑梗死患者阿替普酶静脉溶栓治疗后脑出血性转化的预测价值

摘要 目的：探讨血清尿酸（UA）、同型半胱氨酸（Hcy）和低密度脂蛋白胆固醇（LDL-C）联合监测对急性脑梗死（ACI）患者阿替普酶静脉溶栓治疗后脑出血性转化（HT）的预测价值。方法：选取2018年1月～2020年12月西南医科大学附属成都三六三医院收治的173例接受阿替普酶静脉溶栓治疗的ACI患者,根据静脉溶栓后是否发生HT分为HT组和非HT组。对比两组的临床资料和血清UA、Hcy、LDL-C水平,采用多因素Logistic回归分析ACI患者阿替普酶静脉溶栓治疗后发生HT的影响因素,采用受试者工作特征（ROC）曲线分析血清UA、Hcy、LDL-C联合监测对ACI患者阿替普酶静脉溶栓治疗后发生HT的预测价值。结果：173例患者中有47例发生HT,发生率为27.17％。与非HT组比较,HT组年龄更大,收缩压、舒张压、美国国立卫生研究院卒中量表（NIHSS）评分、溶栓前随机血糖以及Hcy水平更高,而LDL-C及UA水平更低（P＜0.05）。多因素Logistic回归分析结果显示：收缩压、NIHSS评分、溶栓前随机血糖以及Hcy水平为ACI患者阿替普酶静脉溶栓治疗后发生HT的危险因素,而UA、LDL-C水平为保护因素。ROC曲线分析结果显示：血清UA、Hcy、LDL-C单独与联合监测预测ACI患者阿替普酶静脉溶栓治疗后HT的曲线下面积（AUC）分别为0.764、0.794、0.674、0.888,联合监测时的AUC明显更高。结论：血清UA、LDL-C低水平和Hcy高水平是ACI患者阿替普酶静脉溶栓治疗后HT的影响因素,联合监测能提高对HT发生的预测价值。     

下肢深静脉血栓形成的危险因素及导管接触性溶栓的临床疗效研究

目的:分析下肢深静脉血栓形成(DVT)的危险因素,并探讨导管接触性溶栓治疗下肢DVT的临床疗效。方法:选取2015年12月～2018年12月间在北京积水潭医院治疗的126例下肢DVT患者作为病例组,另外选取同期在我院健康体检的志愿者60例作为对照组,采用多因素Logistic回归分析下肢DVT的危险因素。将病例组按随机数表法分为系统溶栓组(采用系统性溶栓治疗)和导管溶栓组(采用导管接触性溶栓治疗)两个亚组,各63例。评价两组疗效,观察两组患者治疗前及治疗1个月后的双下肢周径差和静脉通畅度评分,记录并比较两组患者治疗时间、住院时间、尿激酶用量以及不良反应发生情况。结果:病例组与对照组年龄、体质量指数(BMI)、红细胞计数(RBC)、手术外伤史比较,差异有统计学意义(P0.05)。多因素Logistic回归分析结果显示,年龄、BMI、RBC、手术外伤史均是下肢DVT的独立危险因素(P0.05)。导管溶栓组痊愈率为57.14%(36/63),高于系统溶栓组的33.33%(21/63)(P0.05);治疗1个月后,两组双侧大腿周径差、双侧小腿周径差以及静脉通畅度评分均明显减小,且导管溶栓组上述指标均明显小于系统溶栓组(P0.05)。导管溶栓组治疗时间和尿激酶用量明显少于系统溶栓组,但住院时间明显长于系统溶栓组(P0.05)。两组患者不良反应发生率比较差异无统计学意义(P0.05)。结论:年龄、BMI、RBC、手术外伤史均是下肢DVT的独立危险因素,导管接触性溶栓治疗下肢DVT的疗效显著,具有较好的安全性。     

经皮导管接触溶栓腔内治疗与标准抗凝治疗用于急性下肢深静脉血栓的临床效果比较

目的:分析和比较经皮导管接触溶栓腔内治疗与单纯标准抗凝治疗急性下肢深静脉血栓形成的临床效果的安全性。方法:回顾性分析93例中央型(髂股静脉)和混合型(全下肢深静脉)深静脉血栓患者临床资料,根据治疗方法的不同分为导管溶栓治疗组(试验组)65例、单纯抗凝治疗组(对照组)28例,比较两组患者治疗后患肢消肿率、下肢深静脉血栓的溶栓率及并发症的发生率。结果:治疗后,试验组患者患肢大腿消肿率[(83.03±4.53)%]显著高于对照组[(50.42±7.41)%](P0.05);患肢小腿消肿率[(76.48±8.24)%]亦显著高于对照组(54.95±8.14)%(P0.05)。试验组患者下肢深静脉血栓溶栓有效率为92.31%(60/65),显著高于对照组[14.29%(4/28)](P0.05)。随访半年后,试验组患者下肢血管的通畅率为90.67%(57/65),PTS率为7.69%(5/65);而对照组患者下肢血管的通畅率为21.42%(6/28),PTS率为14.28%(4/28)。试验组血管通畅率明显高于对照组(P0.05),而PTS发生率明显低于对照组(P0.05)。两组患者并发症发生率比较差异无明显统计学意义(P0.05)。结论:经皮导管接触溶栓腔内治疗急性中央型和混合型下肢深静脉血栓的短期疗效优于单纯抗凝治疗,且两种方法的安全性相当。     

Effects of thrombolysis within 6 hours on acute cerebral infarction in an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke

Recombinant tissue plasminogen activator (rt‐PA) is the first‐line drug for revascularization in acute cerebral infarction (ACI) treatment. In this study, an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke was used and the rats were killed on the first, third and seventh day after model establishment. Increases in infarct volume were significantly less in the thrombolytic group than in the conventional group at every time‐point. The microvascular density (MVD) in the thrombolytic group was significantly higher than that in the conventional group at every time‐point, especially on the seventh day. Increases in the expressions of neuronal nitric‐oxide synthase (NOS) and caspase‐3 in the ischaemic region and in the nitric oxide contents, malondialdehyde contents, and inducible NOS activities in the cortex of infarct side were significantly less in the thrombolytic group than in the conventional group. Furthermore, decreases in the superoxide dismutase activities in the thrombolytic group were significantly less than those in the conventional group. In conclusion, thrombolytic rt‐PA therapy within a broadened therapeutic window (6 hours) could significantly decrease the infarct volume after ACI, possibly by increasing MVD in the ischaemic region, decreasing apoptotic molecule expression, and alleviating the oxidative stress response.     

Pathophysiology and Therapy of Experimental Stroke

1. Stroke is the neurological evidence of a critical reduction of cerebral blood flow in a circumscribed part of the brain, resulting from the sudden or gradually progressing obstruction of a large brain artery. Treatment of stroke requires the solid understanding of stroke pathophysiology and involves a broad range of hemodynamic and molecular interventions. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research.2. The first chapter deals with the hemodynamics of focal ischemia with particular emphasis on the collateral circulation of the brain, the regulation of blood flow and the microcirculation. In the second chapter the penumbra concept of ischemia is discussed, providing a detailed list of the physiological, biochemical and structural viability thresholds of ischemia and examples of how these thresholds can be applied for imaging the penumbra. The third chapter summarizes the pathophysiology of infarct progression, focusing on the role of peri-infarct depolarisation, the multitude of putative molecular injury pathways, brain edema and inflammation. Finally, the fourth chapter provides an overview of currently discussed therapeutic approaches, notably the effect of mechanical or thrombolytic reperfusion, arteriogenesis, pharmacological neuroprotection, ischemic preconditioning and regeneration.3. The main emphasis of the review is placed on the balanced differentiation between hemodynamic and molecular factors contributing to the manifestation of ischemic injury in order to provide a rational basis for future therapeutic interventions.     

RGD多肽与尿激酶原嵌合分子的构建及性质研究

利用定点突变及DNA重组技术 ,将编码RGD多肽 (GPRGDWRMLG)的双链DNA片段 ,定向插入到相对于编码尿激酶原的Gly118 Leu119的cDNA分子中 ,构建了尿激酶原的嵌合体基因 ,并在甲醇酵母表达系统中进行了分泌表达。经过Zn²⁺ 螯合柱及SP阳离子柱两步层析后 ,目的蛋白质被纯化。经纤维蛋白平板测活 ,嵌合分子的比活为 6 5 0 0 0IU mg。嵌合分子与尿激酶相比 ,对显色底物S2 44 4作用的催化效率偏低 ,但具有较强的抑制血小板聚集的功能 ,抑制常数IC5 0为 2 1μmol L。以上结果表明嵌合分子不但具有较强的溶栓功能 ,而且具有抗栓功能 ,很可能是一种具有发展前景的双功能溶栓 抗栓分子     

急性缺血性中风早期中小剂量溶栓治疗的初步研究

目的 研究用中、小剂量尿激酶（UK）溶栓治疗急性缺血性中风的临床效果,寻找一个安全的适合静脉溶栓的UK剂量和方法。方法 净急性缺血性中风患者分为两组：溶栓组18例,中小剂量UK溶栓,视病情变化予以追加。常规治疗组（对照组）12例,除不用UK外,其它治疗措施相同。每例患者于治疗前后进行欧洲卒中量表（ESS）评分,以评价疗效。结果 溶栓组溶栓后2h、6h、1天、2天、3天、7天和14天的ESS评分均比溶栓前升高,无并发出血现象,溶栓组治疗后第1天、第2天、第3天、第7天和第14天ESS评分与治疗前ESS评分的差值明显高于常规治疗组治疗后第1天、第2天、第3天、第7天和第14天ESS评分与治疗前ESS评分的差值。结论 用中小剂量UK溶栓,实行剂量个体化,效果较好,且副作用小。     

抗凝血蛋白的抗凝溶栓机制

自然界中存在着大量具有抗凝溶栓活性的生物大分子,如水蛭素、蚓激酶等。这些生物大分子主要是通过抑制凝血酶及凝血因子活性,水解纤维蛋白或纤溶酶原,或是抑制血小板聚集来达到抗凝溶栓的作用。该文对这些活性物质的抗凝溶栓机制进行综述。     

Synergy of in vitro Thrombolytic Action of Combinations of Recombinant Staphylokinase and Single-Chain Urokinase-Type Plasminogen Activator

Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro at 37°C under the influence of recombinant staphylokinase, single-chain urokinase-type plasminogen activator (scu-PA), and their simultaneous and consecutive combinations. Staphylokinase and scu-PA caused concentration- and time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA separately caused 50% lysis in 4 h. At these equally effective concentrations staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma plasminogen, ₂-antiplasmin, and fibrinogen than scu-PA. Combinations of staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action on the clots. The synergy of thrombolytic action was more pronounced on the simultaneous addition of the two agents than on their consecutive addition, scu-PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM) or scu-PA (15 nM) induced 24% and 2% lysis, respectively, whereas the simultaneous and consecutive combination of the same concentrations of these agents induced 58% and 50% lysis, respectively. The simultaneous combination of 15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in the thrombolytic effect as compared to the expected total effect of the individual agents. Synergic combinations of the two agents caused lesser exhaustion of plasma plasminogen, ₂-antiplasmin, and fibrinogen as compared with the expected total effect of these agents used separately. Thus, simultaneous and consecutive combinations of staphylokinase and scu-PA in a relatively narrow range of their concentrations possessed synergistic fibrinselective thrombolytic action on the plasma clot in vitro.