【作者】 田敏；

【导师】 崔元孝；

【作者基本信息】 山东大学 ， 神经病学， 2011， 硕士

【摘要】 高血压性脑出血是临床常见的神经内科急症,发病率和病死率在所有的脑血管病中最高,发病后一个月内的病死率是35～52%,其中50%死于发病后前两天,脑出血病死率与缺血性卒中比较,大约高4～6倍,存活者中50～70%遗留瘫痪、失语等严重残疾,具有发病率高、致死率高和致残率高的特点。急性期病死率高的原因主要是血肿占位效应、血肿周围水肿及颅内高压所致的脑疝形成,因此,外科手术治疗清除血肿是降低死亡率的重要手段之一,微创血肿清除术将显微外科技术与立体定向技术有机结合,具有损伤小,血肿清除率高等优点,广泛应用于高血压性脑出血的治疗。目的通过测定高血压性脑出血微创血肿清除术患者及非手术患者血清组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)的含量,探讨两组患者血液纤溶活性的动态变化；通过比较两组患者病程中不同时点NIHSS评分评价微创血肿清除术治疗高血压性脑出血的临床价值；进一步探讨血清t-PA及PAI-1作为判断微创血肿清除术治疗效果的生物学指标的可靠性。方法选择2008年6月至2009年12月在山东大学附属省立医院神经内科、山东省交通医院神经内科住院的基底节区高血压性脑出血患者89例,出血量30-90ml,分为手术组和非手术组,两组患者均符合入组标准及排除标准,将同期山东大学附属省立医院查体中心健康查体者48名作为正常对照组,手术组和非手术组均常规给予脱水、营养脑细胞、控制血压、控制感染、维持水电解质平衡及其他对症支持治疗,手术组经家属同意后在发病7-24h行颅内血肿微创清除术,选择合适长度的YL-I型一次性颅内血肿穿刺针严格按照“颅内血肿微创清除技术规范化治疗指南”中的要求进行手术。脑出血患者分别于发病后1、3、7、14d采空腹静脉血3ml,正常对照组在体检时采空腹静脉血3ml,离心吸取上层血清置于-80℃冰箱保存待测。采用酶联免疫吸附试验双抗体夹心法(Enzyme-linked immunosorbent assay, ELISA)测定高血压性脑出血手术患者46例、非手术患者43例发病后1、3、7、14d及正常对照组体检时血清t-PA、PAI-1的含量,对各组的t-PA、PAI-1水平进行比较。分别于1、3、7、14d采用美国国立卫生院卒中量表(NIHSS)评定手术组及非手术组患者神经功能缺损程度。采用SPSS11.5统计软件进行数据处理,P<0.05为差异有统计学意义。结果1、血清t-PA和PAI-1的水平变化手术组及非手术组1、3、7d血清t-PA水平显著高于正常对照组(P<0.05),至14d与正常对照组差异无统计学意义,手术组3d、7d血清t-PA水平明显低于非手术组(P<0.05)；手术组3d、7d血清PAI-1水平显著高于正常对照组(P<0.05),至14d血清PAI-1水平与正常对照组差异无统计学意义,手术组1d及非手术组各时间点血清PAI-1水平与正常对照组差异无统计学意义(P>0.05)。2、手术组及非手术组NIHSS评分的变化手术组术后3、7、14d神经功能缺损均较术后1d明显改善(P<0.05),两组患者1d神经功能缺损评分比较差异无统计学意义(P>0.05),3、7、14d神经功能缺损评分比较差异有统计学意义(P<0.05)。3、手术组各时点血清t-PA及PAI-1水平与神经功能缺损的相关关系相关分析显示手术组1、3、7d血清t-PA水平与当天的NIHSS评分成正相关；手术组1、3、7d血清PAI-1水平与当天的NIHSS评分成负相关；14d血清t-PA及PAI-1水平与当天的NIHSS评分无明显相关性。结论高血压性脑出血患者发病早期及微创术后血液纤溶活性存在一定变化规律,血清t-PA、PAI-1可作为判断微创术临床疗效的生物学指标。更多还原

【Abstract】 Hypertensive intracerebral hemorrhage (HICH) is a clinically common and severe disease in Neurology Department, its mobidity and mortality following intracerebral hemorrhage remain the highest among all forms of cerebrovascular diseases, with a 30-day mortality rate of 35～52%, with 50% of the deaths occurring in the first 2 days, HICH is a devastating form of stroke with the high mortality two fold to six fold higher than that for ischemic stroke, therefore HICH is characterized by high mobidity rate, high mortality rate and high disability rate. The main reason of high mortality rate in the acute phase conclude space occupying effect of hematoma, peripheral edema of hematoma and cerebral hernia caused by intracranial hypertension. Therefore, surgical operation is one of the most important measures for decreasing the mortality rate of hypertensive intracerebral hemorrhage. With the development of the microneurosurgery techniques, minimally invasive removal of intracranial hematoma technology is a combination of the microneurosurgery techniques and the stereotaxy techniques, because of its advantages of the minor injuries and the high clearance rate, minimally invasive removal of intracranial hematoma technology is extensively applied in the treatment of hypertensive intracerebral hemorrhage.Objective:To study the dynamical fluctuation of the fibrinolytic activity in hypertensive intracerebral hemorrhage patients with minimally invasive surgery(MIS) through measuring the levels of plasminogen activator inhibitor-1 (PAI-1) antigen and tissue-type plasminogen activator (t-PA). Methods:Choose 89 patients with hypertensive cerebral hemorrhage in basal ganglia area who are in Shandong Provincial Hospital and Shandong Communication Hospital during 2008-2009, quantity of bleeding from 30-90ml, these patients were divided into minimally invasive surgery patient group and non-minimally invasive surgery patient group, both two groups of patients meet the diagnostic criteria and exclusion criteria. Two groups of patients were conventionally given dehydration, blood pressure control, infection control, water and electrolyte balance control and other supporting treatment, within 7-24h after onset and agreed by the family, minimally invasive surgery patient group were given the hematoma minimally invasive surgery with a fit length YL-I type one-time intracranial hematoma puncture needle under local anesthesia in strict accordance with "minimally invasive removal of intracranial hematoma technology standardized treatment guidelines". Blood samples were obtained on days 1,3,7 and 14 after the onset in 46 patients with MIS and 43 patients with non-minimally invasive surgery, and 48 normal controls group, centrifugal extraction of serum placed in the upper -80℃refrigerator prepared test. The levels of plasminogen activator inhibitor-1 (PAI-1) antigen、tissue-type plasminogen activator (t-PA) were measured with an enzyme linked immunosorbent assay (ELISA), neurological function degree were evaluated on days 1,3, 7 and 14 after the onset between minimally invasive surgery patient group and non-minimally invasive surgery patient group. All the analyses were performed using SPSS 11.5 software, Test significance level of P<0.05.Results:1. Changes of serum t-PA and PAI-1 content The level of t-PA in MIS patient group at 1d,3 d and 7 d after onset were significantly higher than those in control group (P<0.05), and there was no significant difference between surgery group and control group at 14 d; The levels of PAI-1 in MIS patient group at 3d, and 7d were significantly higher than those in control group (P< 0.05); The level of t-PA in MIS patient group at 3 d and 7 d were significantly lower than those in non-minimally invasive surgery patient group (P<0.05), The level of PAI-1 in MIS patient group at 3 d and 7 d were significantly higher than those in non-minimally invasive surgery patient group (P<0.05).2. Changes of NIHSS score NIHSS score in MIS patient group at 3d,7d and 14d after onset were significantly lower than those at 1d after onset in MIS patient group (P<0.05), and there was no significant difference between MIS patient group and non-minimally invasive surgery patient group.3. Correlation between the level of t-PA and PAI-1 and NIHSS score in MIS patient group The correlation analysis showed that the level of t-PA in MIS patient group at 1d,3 d and 7 d after onset are positively correlated with the day of NIHSS score, the level of PAI-1 in MIS patient group at 1d,3 d and 7 d after onset are negatively correlated with the day of NIHSS score; The results showed that no significant relativity between the level of t-PA and PAI-1 and NIHSS score in MIS patient group at 14d.Conclusion:Our results support that certain fluctuation regularity of fibrinolytic activity in hypertensive intracerebral hemorrhage patients with minimally invasive surgery exist. The level of t-PA and PAI-1 can be used as the biomakers for clinical outcome in patients with minimally invasive surgery.更多还原