Wang Li, Chen Wei, Peng Zhongjiang, Liu Changcheng, Zhang Caihong, Guo Zhiyong
Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Department of Cell Biology, Division of Basic Medicine, Second Military Medical University, Shanghai 200433, P.R. China.
Mol Med Rep. 2015 Sep;12(3):4291-4297. doi: 10.3892/mmr.2015.3964. Epub 2015 Jun 19.
The present study aimed to examine the effect of the histone deacetylase inhibitor, vorinostat (SAHA), on renal function in a calcium oxalate crystal mouse model, and to investigate the mechanism underlying the renoprotective effect of SAHA. Calcium oxalate crystal formation was induced in 8 week‑old male C57BL/6 mice by administering 100 mg/kg glyoxylate for 7 days. A total of 24 male C57BL/6 mice were randomly divided into a control group and the following experimental groups: 50 mg/kg normal saline + 100 mg/kg glyoxylate; 50 mg/kg dimethyl sulfoxide (DMSO) + 100 mg/kg glyoxylate; and 50 mg/kg SAHA + 100 mg/kg glyoxylate. The mice in each of the experimental groups were injected with the saline, DMSO or SAHA into their abdominal cavities 6 h prior to the glyoxylate injection. The mice were sacrificed after 7 days, following which blood and urine samples were collected. The kidneys were harvested to analyze the levels of calcium concentrations and the levels of malondialdehyde (MDA), superoxide dismutase and glutathione reductase. Immunohistochemical staining and semi‑quantitative analyses were performed to detect the expression levels of osteopontin (OPN) and CD44. Renal tubular cell apoptosis was detected using a TUNEL assay. The concentrations of calcium and malondialdehyde were significantly decreased in the SAHA group, and calcium oxalate crystals in the kidney tissue and the expression levels of OPN and CD44 in the SAHA group were lower, compared with the other experimental groups. SAHA significantly reduced the urinary excretion of KIM‑1 and renal tubular cell apoptosis. In conclusion, SAHA reduced calcium oxalate crystal deposition and protected against kidney injury.
本研究旨在探讨组蛋白去乙酰化酶抑制剂伏立诺他（SAHA）对草酸钙晶体小鼠模型肾功能的影响，并研究SAHA肾脏保护作用的潜在机制。通过给8周龄雄性C57BL/6小鼠连续7天腹腔注射100mg/kg乙醛酸来诱导草酸钙晶体形成。总共24只雄性C57BL/6小鼠被随机分为对照组和以下实验组：50mg/kg生理盐水 + 100mg/kg乙醛酸；50mg/kg二甲基亚砜（DMSO） + 100mg/kg乙醛酸；以及50mg/kg SAHA + 100mg/kg乙醛酸。在注射乙醛酸前6小时，给各实验组小鼠腹腔注射生理盐水、DMSO或SAHA。7天后处死小鼠，随后采集血液和尿液样本。摘取肾脏以分析钙浓度水平以及丙二醛（MDA）、超氧化物歧化酶和谷胱甘肽还原酶的水平。进行免疫组织化学染色和半定量分析以检测骨桥蛋白（OPN）和CD44的表达水平。使用TUNEL检测法检测肾小管细胞凋亡。与其他实验组相比，SAHA组的钙和丙二醛浓度显著降低，SAHA组肾组织中的草酸钙晶体以及OPN和CD44的表达水平较低。SAHA显著降低了KIM-1的尿排泄量和肾小管细胞凋亡。总之，SAHA减少了草酸钙晶体沉积并预防了肾脏损伤。
