Husain Kazim, Suarez Edu, Isidro Angel, Hernandez Wilfredo, Ferder Leon
Kazim Husain, Edu Suarez, Angel Isidro, Leon Ferder, Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine and Health Sciences, Ponce, PR 00732, United States.
World J Biol Chem. 2015 Aug 26;6(3):240-8. doi: 10.4331/wjbc.v6.i3.240.
To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice.
Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses.
ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22(phox), manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals.
Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.
研究帕立骨化醇和依那普利对载脂蛋白E基因敲除小鼠肾脏炎症和氧化应激的保护作用。
将动物分为5组进行为期4个月的治疗,(1)载脂蛋白E基因敲除小鼠加赋形剂组,(2)载脂蛋白E基因敲除小鼠加帕立骨化醇组(每周三次,每次200 ng),(3)载脂蛋白E基因敲除小鼠加依那普利组(30 mg/L),(4)载脂蛋白E基因敲除小鼠加帕立骨化醇加依那普利组,(5)正常小鼠组。采用尾套法记录血压。分离肾脏,用分光光度计进行生化分析和蛋白质印迹分析。
载脂蛋白E缺乏小鼠出现高血压(127±3 mmHg),依那普利以及依那普利加帕立骨化醇治疗可改善高血压,但单独使用帕立骨化醇无效。与正常小鼠相比,载脂蛋白E基因敲除小鼠肾脏丙二醛浓度、p22(phox)、锰超氧化物歧化酶、诱导型一氧化氮合酶(NOS)、单核细胞趋化蛋白-1、肿瘤坏死因子-α和转化生长因子-β1水平显著升高,而谷胱甘肽、铜锌超氧化物歧化酶和内皮型一氧化氮合酶水平显著降低。给予帕立骨化醇、依那普利及其联合用药可改善载脂蛋白E基因敲除小鼠的肾脏炎症和氧化应激。
帕立骨化醇和依那普利联合治疗可改善动脉粥样硬化动物的肾脏炎症和氧化应激。