肢体缺血再灌注与血小板聚集活性的关系：健康志愿者临床观察

发布时间：2018-05-18 17:40

本文选题：心脏远隔预适应 + 缺血再灌注　；参考：《天津医科大学》2010年硕士论文

【摘要】： 背景：对骨骼肌进行暂时性的缺血再灌注,能够产生类似缺血预适应的心脏保护作用,这一现象称为“心脏远隔缺血预适应”(cardiac remote ischemic preconditioning)。但间断重复阻断骨骼肌血流会在一定程度上引起骨骼肌的生化微环境的变化,进而有可能会对循环血小板的聚集活性产生影响。对于上述问题,尚未见到相关研究报道。目的：旨在观察健康志愿者中,骨骼肌暂时性缺血再灌注处理对循环血小板体外聚集活性的干预作用,并探讨其有关影响因素。方法：在中国人民武装警察部队医学院附属医院共招募31名健康志愿者,操作流程经医院伦理委员会通过,所有受试者签署知情同意书。采用血压计袖带束缚单侧上肢后,将压力维持在200mmHg,采用3个5min-5min缺血-再灌注循环的标准操作流程实现骨骼肌的缺血再灌注。采集受试者基线、缺血再灌注后60min,以及缺血再灌注后24小时静脉血进行血小板聚集活性测试(ADP诱导的比浊法)、有关血生化检测；采用ELISA法测定各时点组织因子(tissue factor,TF)、高敏C反应蛋白(high sensitive C reactive protein, hsCRP)、肌红蛋白以及纤溶酶原激活物抑制因子-1(plasminogen activator inhibitor-1,PAI-1)水平变化。结果：按照纳入排除标准,最后24名完成所有测试的受试者数据纳入分析。其中女性8人,男性16人,平均年龄30.7±1.4岁,平均腰臀比0.84±0.1,平均体重指数(body mass index)22.1±0.5 Kg/m2。24名受试者均完成所有采血。所有受试者在进行上肢缺血再灌注处理过程中,未报告明显肢体局部或全身不适感。在进行肢体缺血再灌注处理前后,血钾水平未发现明显变化(缺血前,缺血后60min以及缺血24h后,分别对应4.5±0.1 mmol/L,4.5±0.1 mmol/L和4.4±0.1mmol/L,P=0.568)。此外,PAI-1水平也未出现明显动态变化(14.6±0.2ng/mL,14.6±0.3 ng/mL,14.5±0.2 ng/mL,P=0.848)。血浆总组织因子水平呈现明显的动态变化趋势：表现为骨骼肌缺血再灌注后(60min)立即增高,24小时后逐渐回落至基线水平(与基线水平比较无差异),且60min后与基线水平和24小时后比较均有统计学差异。在肢体缺血再灌注处理60min后,受试者整体血小板聚集活性离散趋势明显增大,提示存在个体血小板反应的异质性。按照血小板的聚集率的不同,个体血小板的反应性定义为在肢体缺血再灌注处理之后60min的聚集活性与基线聚集活性的差值(ΔAggregation,ΔA),如ΔA=10%,则此个体定义为高反应者：其余个体定义为无/低反应者。高反应者共6人,其中女性1人,男性5人；无/低反应者共18人,其中女性7人,男性11人。缺血再灌注处理之前,两组人群的所有研究指标之间均未见统计学差异。此外,缺血后24小时,各项指标之间亦未见统计学差异。hsCRP在骨骼肌缺血再灌注60min后,在高反应组和无低反应组中存在差异(高反应组2.0±0.3 mg/L v.s.无/低反应组2.9±0.2 mg/L,P=0.026)。尤其值得注意的是,血循环hsCRP的变化量(ΔhsCRP,即再灌注后60min的hsCRP与基线hsCRP的差值)在两组之间也存在统计学差异(高反应组0.28±0.11 mg/L v.s.无/低反应组-0.38±0.31 mg/L,P=0.016)；而24小时后,上述影响基本回复至基线水平(高反应组2.2±0.4mg/L v.s无/低更应组2.8±0.2mg/L,P=0.149)ΔhsCRP与AA呈现负相关关系(r=-0.411,P=0.046)。结论：总体而言,骨骼肌缺血再灌注处理对循环血小板的聚集活性无明显影响,但可引起循环总组织因子水平的一过性增高。健康人群中的血小板的聚集活性对暂时性骨骼肌缺血再灌注存在异质性,尤其是血小板聚集活性高反应者在骨骼肌缺血后60min循环CRP水平增高不明显,明显低于无/低反应者。
[Abstract]:Background: temporary ischemia-reperfusion of skeletal muscles can produce a protective effect similar to ischemic preconditioning. This phenomenon is called cardiac remote ischemic preconditioning. However, intermittent repetitive blocking of skeletal muscle blood flow can cause the biochemical microenvironment of skeletal muscle to a certain extent. It is possible that the aggregation activity of circulating platelets may be affected.
Objective: To observe the effect of temporary ischemia reperfusion on the extracorporeal platelet aggregation activity of circulating platelets in healthy volunteers, and to explore the related factors.
Methods: a total of 31 healthy volunteers were recruited in the Affiliated Hospital of the Chinese people's armed police force. The operation process was passed through the hospital ethics committee. All the subjects signed the informed consent. After using the cuff of the sphygmomanometer, the pressure was maintained at 200mmHg and the standard operation of 3 5min-5min ischemia reperfusion cycles was used. The flow of ischemic reperfusion of skeletal muscle was realized. Baseline of the subjects, 60min after ischemia-reperfusion, and 24 hours after ischemia and reperfusion were tested for platelet aggregation activity (ADP induced turbidimetry), blood biochemical test, and ELISA assay (tissue factor, TF), and high sensitive C reactive protein (high sensit). Ive C reactive protein (hsCRP), myoglobin and plasminogen activator inhibitor -1 (plasminogen activator inhibitor-1, PAI-1) level changes.
Results: according to the exclusion criteria, the final 24 subjects completed all the test data into the analysis. Among them, 8 were women, 16 men were male, the average age was 30.7 + 1.4, the average waist hip ratio was 0.84 + 0.1, the average body mass index (body mass index) 22.1 + 0.5 Kg/m2.24 subjects all completed all blood collection. All the subjects were in the upper limb ischemia and reperfusion. During the perfusion treatment, there was no obvious local or systemic discomfort. There was no obvious change in the level of blood potassium before and after ischemia and reperfusion (ischemia, 60min and 24h, respectively, 4.5 + 0.1 mmol/L, 4.5 + 0.1 mmol/L and 4.4 + 0.1mmol/L, P=0.568). Besides, there was no obvious movement of PAI-1. State changes (14.6 + 0.2ng/mL, 14.6 + 0.3 ng/mL, 14.5 + 0.2 ng/mL, P=0.848). The plasma total tissue factor level showed a significant trend of dynamic change: the expression of skeletal muscle ischemia reperfusion (60min) immediately increased, after 24 hours gradually fall to the baseline level (compared with baseline water level no difference), and 60min after the baseline level and 24 hours after the ratio. There were statistical differences.
After the treatment of 60min, the trend of the platelet aggregation activity in the subjects increased significantly, suggesting the heterogeneity of the individual platelet reaction. According to the platelet aggregation rate, the individual platelet reactivity was defined as the aggregation activity of 60min and the baseline aggregation activity after the limb ischemia reperfusion treatment. The difference (delta Aggregation, Delta A), such as delta A=10%, was defined as a high response person: the rest of the individual was defined as a non / low response person. A total of 6 high responders, of which 1 were female, 5 men, and 18 were no / low response, including 7 women and 11 men. Before the ischemia reperfusion treatment, no statistics were found among all the research indicators of the two groups. In addition, 24 hours after ischemia, there was no statistical difference between the indexes and.HsCRP after skeletal muscle ischemia reperfusion 60min, there was a difference between the high reaction group and the no low reaction group (the high reaction group was 2 + 0.3 mg/L v.s. no / low reaction group, 2.9 + 0.2 mg/L, P=0.026). The difference between the hsCRP of 60min and the baseline hsCRP after reperfusion was also statistically different between the two groups (the 0.28 + 0.11 mg/L v.s. without / -0.38 + 0.31 mg/L, P=0.016) in the high reaction group, and the above effect was basically returned to the baseline level after 24 hours (2.2 + 0.4mg/L v.s without / low in the high response group, 2.8 + 0.2mg/L, P=0.149) A showed a negative correlation (r=-0.411, P=0.046). Conclusion: in general, skeletal muscle ischemia reperfusion treatment has no obvious effect on the aggregation activity of circulating platelets, but it can cause an excessive increase in the level of circulating total tissue factors. The aggregation activity of platelet in healthy people is heterogeneous in transient skeletal muscle ischemia reperfusion. The high level of platelet aggregation activity in the 60min cycle after skeletal muscle ischemia increased CRP level was not obvious, significantly lower than those with no / low response.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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