| Summary: | 碩士 === 高雄醫學大學 === 藥學研究所碩士在職專班 === 101 === Background: Stroke is a major cause of serious morbidity and mortality in the worldwide. Inflammation and oxidative stress play pivotal role in acute ischemic stroke. Acute ischemic stroke (AIS) leads to a complicated cascade of events involving cerebral ischemia, inflammation, neuronal necrosis, and apoptosis of the blood-brain barrier; and neurological dysfunction. Endothelial repair and neo-vascularization are possible recovering from ischemic stroke in the adult brain.
The endothelial progenitors cells (EPCs), released from bone marrow to circulation, characterized by the expression of cell markers CD34, CD133 and vascular endothelial growth factor receptor (VEGF-R). EPCs have been demonstrated in both animal models and humans to contribute to neo-vascularization and re-endothelialization. The clinical studies demonstrated that cardiovascular diseases are associated with dysfunction of EPCs, and the numbers of circulating EPCs is correlated positively with cardiovascular outcome.
Statins, the 3-hydroxy 3-methyl-glutaryl coenzyme-A reductase inhibitors, are originally used for treatment of hypercholesterolemia. The accumulating evidences have suggested that statins possess pleiotropic effects, which include the improvement of endothelial function and an anti-thrombotic effect, independent of their impact on cholesterol-lowering effect. Statin therapy has been shown to reduce cardiovascular events, including myocardial infarction, stroke, and death. In vitro studies, statins have been found to enhance the mobilized and proliferative capacity of EPCs. However, the role of statin therapy on circulating EPCs in patients with AIS has not been well studied. This study aimed to evaluate the relationship among the statin therapy, serial changes of circulating EPCs and outcome in patients after AIS.
Methods: This prospective study evaluated 65 patients with AIS (26 patients with statin therapy and 39 without statin therapy). The circulating level of EPCs (CD133+/CD34+ and KDR+/CD34+) were determined using flow cytometry at different time points (within 48 hours and Day 7, 30 days post-stroke) and analyzed with clinical outcome. EPCs level was also evaluated once in 65 risk control group.
Results: The level of CD133+/CD34+ and KDR+/ CD34+ EPCs were significantly lower in AIS groups when compared to those in the control groups (p<0.05). The level of CD133+/CD34+ EPCs was significantly lower in the large vessel disease group when compared to small vessel disease group on Day 1 after acute stroke (p<0.05). Then, the level of CD133+/CD34+ EPCs was gradually increased thereafter and similar between these two groups on Day 7 after ischemic stroke. The number of circulating EPCs was not significantly different between the patients with and without statin therapy. Statistical analysis revealed that subtype of stroke, diastolic BP, level of CD133+/CD34+ and KDR+/CD34+ EPCs on admission were significantly different between the good and poor outcome groups. After adjustments for covariance using stepwise logistic regression, only subtype of stroke (OR=30.2, 95% CI=5.3-171.4; p<0.001) and KDR+/CD34+ on admission (OR=0.188, 95% CI=0.04-0.86; p=0.031) were independently associated with six-month outcome.
Conclusions: The number of circulating EPCs was significantly lower in the large vessel disease than in the small vessel disease group at acute stage of ischemic stroke. Statins do not significant affect the circulating EPCs in patients after AIS. The lower number of EPCs is an independent risk factor for poor six-month outcome in patients after AIS.
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