Zheng Yi, Zhang Zhewei, Zhang Nan
Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,
Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Urol Int. 2019;102(3):348-355. doi: 10.1159/000497476. Epub 2019 Mar 7.
Renal ischemia-reperfusion injury (IRI) usually causes acute kidney injury. There is an urgent need to develop an effective agent to prevent renal IRI. This study aimed to examine the effect of butyrate on renal IRI in rats.
Rats were randomly assigned into 3 groups (10 rats in each group): the sham group, the IRI group, and the butyrate group. Rats were injected intravenously with 300 mg/kg of sodium butyrate in the butyrate group and with a saline solution in the sham group and IRI group 30 min before renal ischemia. After 24 h of reperfusion, renal function and histologic damage were examined. Myeloperoxidase (MPO) activity assay, in situ apoptosis examination, enzyme-linked immunosorbent assay, immunohistochemical assay, and Western blot were performed as well.
Butyrate pretreatment significantly reduced renal dysfunction and histologic damage induced by renal IRI. Butyrate pretreatment caused a significant attenuation of neutrophil infiltration, which was reflected by the reduction of renal MPO activity. Butyrate also reduced apoptotic tubular cell death and improved caspase-3 activation. The expression of TNF-α was decreased following butyrate pretreatment.
Butyrate pretreatment protects rats from renal IRI by inhibiting inflammation and apoptosis. Therefore, butyrate may be a potential therapeutic agent for preventing renal IRI.
肾缺血再灌注损伤(IRI)通常会导致急性肾损伤。迫切需要开发一种有效的药物来预防肾IRI。本研究旨在探讨丁酸盐对大鼠肾IRI的影响。
将大鼠随机分为3组(每组10只):假手术组、IRI组和丁酸盐组。在肾缺血前30分钟,丁酸盐组大鼠静脉注射300mg/kg丁酸钠,假手术组和IRI组大鼠静脉注射生理盐水。再灌注24小时后,检测肾功能和组织学损伤。还进行了髓过氧化物酶(MPO)活性测定、原位凋亡检测、酶联免疫吸附测定、免疫组织化学测定和蛋白质印迹分析。
丁酸盐预处理显著减轻了肾IRI诱导的肾功能障碍和组织学损伤。丁酸盐预处理导致中性粒细胞浸润显著减轻,这通过肾MPO活性的降低得以体现。丁酸盐还减少了凋亡性肾小管细胞死亡并改善了半胱天冬酶-3的激活。丁酸盐预处理后肿瘤坏死因子-α的表达降低。
丁酸盐预处理通过抑制炎症和凋亡保护大鼠免受肾IRI损伤。因此,丁酸盐可能是预防肾IRI的一种潜在治疗药物。