Gholamzadeh Raheleh, Eskandari Mehdi, Bigdeli Mohammad Reza, Mostafavi Hossein
Department of Physiology and Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Animal Science, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran.
Basic Clin Neurosci. 2018 Sep-Oct;9(5):347-356. doi: 10.32598/bcn.9.5.347. Epub 2018 Sep 1.
Brain Ichemic-Reperfusion Injury (IRI) activates different pathophysiological processes. It also changes physiological parameters such as Blood Glucose (BG) level. An increase in BG after stroke is associated with poor clinical outcomes. Erythropoietin has been shown to be effective on both reducing inflammation and BG level. Therefore, in this study the erythropoietin pretreatment effect on BG and its relationship with inflammatory markers after brain IRI was investigated.
Thirty adult male Wistar rats were randomly divided into 5 groups: sham, control and 3 pretreatment groups: single dose, double dose, and triple dose that received 1000 U/kg of erythropoietin before stroke induction in different times intraperitoneally. A rat model of IRI was established by Middle Cerebral Artery Occlusion (MCAO) for 60 minutes. Infarct volume, neurological defects, Interleukin-1α (IL-1α) and IL-6 serum levels were evaluated 24 hours after reperfusion. Also BG was measured after 1, 6, and 24 hours.
Single dose of erythropoietin significantly decreased infarct volume and improved neurological defects which was associated with decreased serum level of IL-1α and IL-6 but higher doses of erythropoietin administration had adverse effects on histological, neurological, and inflammatory results. In addition, erythropoietin significantly increased BG in a dose-dependent manner.
Erythropoietin could reduce brain IRI by reducing inflammation and BG stabilization. The results of the present study demonstrated a relationship between inflammatory factors and hyperglycemia after IRI and suggested that erythropoietin may be useful for preventing brain IRI, but its higher doses should be used with caution due to possible side effects.
脑缺血再灌注损伤（IRI）会激活不同的病理生理过程。它还会改变诸如血糖（BG）水平等生理参数。中风后血糖升高与不良临床预后相关。已证明促红细胞生成素在减轻炎症和降低血糖水平方面均有效。因此，在本研究中，研究了促红细胞生成素预处理对脑IRI后血糖的影响及其与炎症标志物的关系。
30只成年雄性Wistar大鼠随机分为5组：假手术组、对照组和3个预处理组：单剂量组、双剂量组和三剂量组，在不同时间腹腔内给予1000 U/kg促红细胞生成素，然后诱导中风。通过大脑中动脉闭塞（MCAO）60分钟建立IRI大鼠模型。再灌注24小时后评估梗死体积、神经功能缺损、白细胞介素-1α（IL-1α）和IL-6血清水平。此外，在1、6和24小时后测量血糖。
单剂量促红细胞生成素显著降低梗死体积并改善神经功能缺损，这与血清IL-1α和IL-6水平降低相关，但更高剂量的促红细胞生成素给药对组织学、神经学和炎症结果有不良影响。此外，促红细胞生成素以剂量依赖方式显著升高血糖。
促红细胞生成素可通过减轻炎症和稳定血糖来减轻脑IRI。本研究结果表明IRI后炎症因子与高血糖之间存在关联，并提示促红细胞生成素可能有助于预防脑IRI，但由于可能的副作用，应谨慎使用更高剂量。
