Tahamtan Mahshid, Sheibani Vahid, Shid Moosavi Seyed Mostafa, Asadi-Shekaari Majid, Esmaeili-Mahani Saeed, Aghaei Iraj, Shabani Mohammad
Intracellular Recording Lab, Kerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
Physiology Department, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Pharm Res. 2018 Spring;17(2):601-612.
One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI). Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham +V (Vehicle), 3, 4) Sham+EPO, 5, 6) BRI+V, 7, 8) BRI+EPO. The groups followed by the reperfusion periods of 24hours (24 h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p). The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Hippocampal brain-derived neurotrophic factor (BDNF) protein expression was assessed by western blotting. BUN (blood urea nitrogen) and creatinine (Cr) concentrations were significantly increased in BRI+V group 24 h after reperfusion. BRI+V rats had just an increased level of BUN but not Cr 1w after reperfusion. EPO reversed passive avoidance learning impairments observed in BRI+V group 24 h after reperfusion. There were no significant differences in spatial and passive avoidance learning between experimental groups 1w after reperfusion and histological evaluation confirmed the behavioral data. BRI significantly decreased the BDNF protein expression in the hippocampus and EPO increased that 24 h after operation. These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24 h after reperfusion through increase in BDNF protein expression.
急性肾损伤最常见的死亡原因之一是脑功能障碍。在此,我们研究了促红细胞生成素(EPO)对双侧肾缺血(BRI)所致认知障碍的可能保护作用。80只雄性Wistar大鼠被分为8组:1、2)假手术+V(溶剂)组,3、4)假手术+EPO组,5、6)BRI+V组,7、8)BRI+EPO组。这些组分别经历24小时(24 h)和1周(1w)的再灌注期。在手术前30分钟给予EPO或生理盐水(1000 IU/kg,腹腔注射)。通过被动回避学习和莫里斯水迷宫试验评估认知功能。通过蛋白质印迹法评估海马脑源性神经营养因子(BDNF)蛋白表达。再灌注24小时后,BRI+V组的血尿素氮(BUN)和肌酐(Cr)浓度显著升高。再灌注1周后,BRI+V大鼠的BUN水平升高,但Cr水平未升高。EPO逆转了再灌注24小时后BRI+V组观察到的被动回避学习障碍。再灌注1周后,实验组之间的空间和被动回避学习没有显著差异,组织学评估证实了行为学数据。BRI显著降低海马中BDNF蛋白表达,而EPO在术后24小时增加了该蛋白表达。这些观察结果表明,EPO通过增加BDNF蛋白表达对再灌注24小时后BRI所致的认知功能障碍具有保护作用。