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Effect of Different Doses and Times of FK506 on Different Areas of the Hippocampus in the Rat Model of Transient Global Cerebral Ischemia-Reperfusion

机译:FK506不同剂量和时间的影响在瞬时全球脑缺血再灌注大鼠大鼠大鼠模型中不同区域的影响

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Background. Stroke is a major worldwide problem that is leading to a high mortality rate in humans. Ischemia, as the most common type of stroke, is characterized by tissue damage that can occur due to insufficient blood flow to the brain even for a brief duration, leading to the release of inflammatory factors, cytokines, and free radicals. In this study, we investigated the effective dose and injection time of FK506 as an immunophilin ligand for providing a suitable effect on cells of CA2, CA3, and dentate gyrus of the hippocampus. Methods. In this in vivo study, a total of 48 male Wistar rats were divided into nine groups. The ischemia model was induced by the ligation of bilateral common carotid arteries. The doses of FK506 (3, 6, and 10 mg/kg) were administered intravenously (IV) at the beginning of reperfusion, followed by repeated injections (10 mg/kg) at 6, 24, 48, and 72 hours after ischemia, respectively. Brains were removed and prepared for Nissl staining and the TdT-mediated dUTP Nick End Labeling method. Results. Data showed that global ischemia did not decrease the number of viable pyramidal cells in CA2 and CA3 regions, but significant differences were observed in the number of viable granular cells and apoptotic bodies in the dentate gyrus between the control and ischemia groups. Repeated doses of 6 mg/kg of FK506 at an interval of 48 hours were deemed to be the suitable dose and best time of injection. Conclusions. It seems that FK506 can ameliorate the extent of apoptosis and may be a good candidate for the treatment of ischemia-induced brain damage.
机译:背景。中风是一个主要的全球问题,导致人类的高死亡率。作为最常见的中风类型的缺血,其特征在于由于甚至在短暂的持续时间内,由于血流不足而可能发生的组织损伤,导致炎症因素,细胞因子和自由基的释放。在该研究中,我们研究了FK506作为免疫蛋白配体的有效剂量和注射时间,用于为海马的Ca2,Ca,Ca 3和牙齿诱导的细胞提供合适的效果。方法。在这种情况下,共有48只雄性Wistar大鼠分为九组。通过双侧常见的颈动脉结扎诱导缺血模型。在再灌注开始时静脉内(IV)施用FK506(3,6和10mg / kg),然后在缺血后6,24,48和72小时重复注射(10mg / kg),分别。除去大脑并为NISSL染色和TDT介导的DUTP切口末端标记方法制备。结果。数据显示全局缺血未降低Ca2和Ca3区中的活锥细胞的数量,但在对照和缺血基团之间的牙齿血液细胞和凋亡体中观察到显着差异。以48小时的间隔重复为6mg / kg fk506的剂量,被认为是合适的剂量和最佳注射时间。结论。似乎FK506可以改善细胞凋亡的程度,可能是治疗缺血诱导的脑损伤的良好候选者。

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