Xie Guangliang, Liu Shusu, Zhang Qiannan, Zhang Wenli, Zhu Lin, Zhang Yanmin, Yu Qing
Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 200437, China.
Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine Shanghai 201620, China.
Am J Transl Res. 2020 Jul 15;12(7):3402-3411. eCollection 2020.
This study sought to investigate the effectiveness of hepcidin in renal ischemia/reperfusion injury by using a rat model of renal IRI.
In our study, male Sprague-Dawley rats were divided into a hepcidin-treated group and a control group before establishing the animal models. According to the difference of the modelling methods (renal pedicle occlusion for 45 minutes or not) and renal reperfusion time, the rats were then respectively divided into four subgroups: sham, IRI 4 h, IRI 12 h, and IRI 24 h. After the establishment of the IRI model, the rats were killed to determine renal function, histology, iron metabolism indexes in plasma and tissues, and the expression level of hepcidin and ferroportin-1.
The results indicated that the levels of serum creatinine, blood urea nitrogen and serum iron, the renal iron content, and the kidney injury score were significantly decreased in the hepcidin group (<0.05). The serum hepcidin and the splenic iron content were significantly increased while the duodenal iron content was significantly decreased in the hepcidin group (<0.05). Hepcidin expression in the liver and ferroportin-1 expression in the kidneys were significantly decreased in the hepcidin group (<0.05).
Hepcidin has a reno-protective effect in renal IRI by possibly promoting iron intake in the spleen, inhibiting iron absorption and exportation in the duodenum, alleviating the degree of serum iron, and reducing renal iron accumulation in the renal IRI.
本研究旨在通过使用肾缺血/再灌注损伤大鼠模型来探究铁调素在肾缺血/再灌注损伤中的有效性。
在我们的研究中,雄性Sprague-Dawley大鼠在建立动物模型前被分为铁调素治疗组和对照组。根据建模方法(肾蒂阻断45分钟与否)和肾再灌注时间的差异,大鼠随后被分别分为四个亚组:假手术组、缺血/再灌注4小时组、缺血/再灌注12小时组和缺血/再灌注24小时组。在建立缺血/再灌注损伤模型后,处死大鼠以测定肾功能、组织学、血浆和组织中的铁代谢指标以及铁调素和铁转运蛋白-1的表达水平。
结果表明,铁调素组血清肌酐、血尿素氮和血清铁水平、肾铁含量以及肾损伤评分均显著降低(<0.05)。铁调素组血清铁调素和脾脏铁含量显著升高,而十二指肠铁含量显著降低(<0.05)。铁调素组肝脏中铁调素表达和肾脏中铁转运蛋白-1表达均显著降低(<0.05)。
铁调素在肾缺血/再灌注损伤中具有肾保护作用,可能是通过促进脾脏铁摄取、抑制十二指肠铁吸收和输出、减轻血清铁程度以及减少肾缺血/再灌注损伤中的肾铁蓄积来实现的。