摘要
本研究旨在通过探讨氧嗪酸钾的不同给药方式,并联合次黄嘌呤构建一种高效的高尿酸血症肾病(hyperuricemic nephropathy,HN)小鼠模型,并对模型效果进行评价。动物福利和实验过程均遵循广东药科大学动物伦理委员会的规定。选取雄性C57BL/6小鼠随机分为正常对照组、氧嗪酸钾(灌胃给药100 mg·kg^(-1)·d^(-1))+次黄嘌呤(灌胃给药500 mg·kg^(-1)·d^(-1))模型组、氧嗪酸钾(腹腔注射给药100 mg·kg^(-1)·d^(-1))+次黄嘌呤(灌胃给药500 mg·kg^(-1)·d^(-1))模型组,每天给药1次,持续给药21天诱导HN模型。血液生化结果表明,与正常对照组相比,灌胃氧嗪酸钾联合次黄嘌呤小鼠血清中尿酸、肌酐水平及24 h尿蛋白含量明显提升(P<0.05),肝脏黄嘌呤氧化酶水平无明显差异;腹腔注射氧嗪酸钾联合灌胃次黄嘌呤小鼠血清中尿酸最高值达到349.3μmol·L^(-1),肌酐最高达到26.4μmol·L^(-1),肝脏黄嘌呤氧化酶水平及24 h尿蛋白含量也显著提升(P<0.01)。肾脏病理结果显示,灌胃氧嗪酸钾联合次黄嘌呤小鼠部分肾小管扩张,肾小管上皮细胞排列紊乱,出现部分胶原纤维,活性氧和脂质过氧化物4-羟基壬烯醛(4-HNE)生成轻微增加;而腹腔注射氧嗪酸钾联合灌胃次黄嘌呤小鼠出现明显的炎症细胞浸润和大面积的胶原沉积,产生了大量活性氧和4-HNE。Western blot结果显示,与灌胃氧嗪酸钾联合灌胃次黄嘌呤小鼠纤维黏连蛋白(FN)和尿酸转运蛋白1(URAT1)的蛋白表达增加相比,腹腔注射氧嗪酸钾联合灌胃次黄嘌呤小鼠可进一步增加FN和URAT1的表达。本研究证实,腹腔注射100 mg·kg^(-1)氧嗪酸钾联合灌胃500 mg·kg^(-1)次黄嘌呤可建立更高效的高尿酸血症肾病小鼠模型。
The aim of this study was to establish an efficient and stable mouse model of hyperuricemic nephropathy(HN)by testing different modes of administration of potassium oxonate(PO)combined with hypoxanthine(Hx).Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guangdong Pharmaceutical University.Male C57BL/6 mice were randomly divided into a control group,a PO+Hx group(i.g.;100 mg·kg^(-1)·d^(-1) and 500 mg·kg^(-1)·d^(-1),respectively),and a PO+Hx group(i.p.;100 mg·kg^(-1)·d^(-1),and 500 mg·kg^(-1)·d^(-1)).This HN model was induced by combination of PO and Hx administration once daily for 21 days.The results of serum biochemistry showed that the levels of serum creatinine and 24 h albuminuria were increased compared with the normal group in intragastric administration of PO combined with Hx(P<0.05),but there was no significant difference in serum uric acid and hepatic levels of xanthine oxidase.The maximum value of serum uric acid and creatinine was 349.3μmol·L^(-1) and 26.4μmol·L^(-1),respectively,in mice injected with PO combined with Hx.The levels of liver xanthine oxidase and 24 h albuminuria were significantly increased in mice injected with PO combined with Hx(P<0.01).Pathological data showed that renal tubules were dilated,the epithelial cells of renal tubules were disordered,and the production of collagen fibers,reactive oxygen species(ROS)and lipid peroxidase 4-hydroxynonenal(4-HNE)were slightly increased after intragastric administration of PO combined with Hx mice.Obvious infiltration of inflammatory cells and large area of collagen deposition,with a large amount of ROS and the lipid peroxide 4-HNE were produced in mice injected with PO combined with Hx.Western blot analysis showed that the expression of fibronectin(FN)and urate transporter 1(URAT1)was increased after intragastric administration of PO combined with Hx in mice and further increased in mice injected with PO combined with Hx.This study demonstrates that injection wi
作者
李明慧
吴铠礽
陈哲
孙蕾妍
黄晓其
胡旭光
兰天
LI Ming-hui;WU Kai-reng;CHEN Zhe;SUN Lei-yan;HUANG Xiao-qi;HU Xu-guang;LAN Tian(Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangzhou University of Chinese Medicine,Guangzhou 510006,China)
出处
《药学学报》
CAS
CSCD
北大核心
2022年第6期1673-1678,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81870420,82070590)。
关键词
氧嗪酸钾
高尿酸血症肾病
氧化应激
次黄嘌呤
炎症
potassium oxonate
hyperuricemic nephropathy
oxidative stress
hypoxanthine
inflammation
