Department of Anatomy, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada, Yogyakarta, Indonesia.
Kobe J Med Sci. 2020 Mar 9;65(4):E138-E143.
The incidence rate of Acute Kidney Injury (AKI) gets escalated each year. Kidney ischemia/reperfusion injury (IR injury) is the main cause of AKI after major cardiovascular surgery, trauma, or kidney transplantation. Reperfusion is considered essential for ischemic tissue. However, the evidence revealed that reperfusion itself has impact in cellular destruction. Vitamin D is not only known as calcium regulating hormone, but also as renoprotective agent. This study aimed to investigate the effect of vitamin D treatment on kidney IR injury in mice. Kidney IR injury was performed using 30 minutes of bilateral clamping of renal pedicles, then released in male Swiss Webster mice (3 months, 30-40 grams, n=20), which were divided into three groups: sham operation (SO) group, IR injury (IRI) group, and IR injury with 0.25 µg/ kg body weight of vitamin D treatment (IR7+VD). Mice were terminated at day 7 post operation, kidneys were harvested and used for paraffin making, immunostaining and RNA extraction. Tubular injury was quantified based on Periodic Acid-Schiff's (PAS) staining. Immunostaining was done for quantification of macrophage (CD68) and myofibroblast (α-SMA). Reverse Transcriptase PCR (RT-PCR) was done to examine Monocyte Chemoattractant Protein-1 (MCP-1) and Toll-like Receptor 4 (TLR4) mRNA expression. Kidney IR injury induced significant increase of tubular injury, which was associated with higher myofibroblast and macrophage number. Meanwhile, Vitamin D treatment significantly reduced tubular, myofibroblast and macrophage number. RTPCR revealed reduction of TLR4 and MCP-1 mRNA expressions after Vitamin D treatment (p<0.05 vs IR group). Vitamin D ameliorates kidney IR injury through reducing inflammation and myofibroblast formation.
急性肾损伤(AKI)的发病率逐年上升。肾缺血/再灌注损伤(IR 损伤)是大血管手术后、创伤后或肾移植后 AKI 的主要原因。再灌注被认为对缺血组织是必不可少的。然而,有证据表明,再灌注本身对细胞破坏有影响。维生素 D 不仅是一种调节钙的激素,也是一种肾保护剂。本研究旨在探讨维生素 D 治疗对小鼠肾 IR 损伤的影响。采用双侧肾蒂夹闭 30 分钟的方法建立肾 IR 损伤模型,然后在雄性瑞士 Webster 小鼠(3 个月,30-40 克,n=20)中释放,将其分为三组:假手术(SO)组、IR 损伤(IRI)组和 IR 损伤加 0.25μg/ kg 体重维生素 D 治疗(IR7+VD)组。术后第 7 天处死小鼠,取肾脏进行石蜡包埋、免疫染色和 RNA 提取。根据过碘酸希夫(PAS)染色定量肾小管损伤。免疫染色用于定量检测巨噬细胞(CD68)和肌成纤维细胞(α-SMA)。逆转录聚合酶链反应(RT-PCR)用于检测单核细胞趋化蛋白-1(MCP-1)和 Toll 样受体 4(TLR4)mRNA 表达。肾 IR 损伤诱导肾小管损伤显著增加,与肌成纤维细胞和巨噬细胞数量增加相关。同时,维生素 D 治疗可显著减少肾小管、肌成纤维细胞和巨噬细胞数量。RT-PCR 显示维生素 D 治疗后 TLR4 和 MCP-1mRNA 表达减少(与 IR 组相比,p<0.05)。维生素 D 通过减少炎症和肌成纤维细胞形成改善肾 IR 损伤。