羟苯磺酸钙对对比剂肾病大鼠肾的保护作用Protective effects of calcium dobesilate on Contrast-induced nephropathy in rats
于芬芬,季文萱,单文红,孙艳,刘桂美,黄俊彦
摘要(Abstract):
目的探讨羟苯磺酸钙对对比剂肾病(CIN)模型大鼠的影响。方法将84只大鼠随机分为3组:假手术组(A组)、模型组(B组)和羟苯磺酸钙干预组(C组)。B组和C组分别注射吲哚美辛(INDO)、N-硝基-L-精氨酸甲酯(L-NAME)和76%泛影葡胺建立CIN大鼠模型;A组注射等量INDO+L-NAME+生理盐水;C组于造模前3 d及造模当天给予羟苯磺酸钙[100 mg/(kg·d)]灌胃,A组及B组给予等量生理盐水灌胃。于造模后24 h、48 h、72 h分别处死大鼠(每组7只),取血和肾组织,测定血尿素氮(BUN)、肌酸酐(Scr),HE染色观察肾病理改变;ELISA法检测血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的含量;TUNEL染色检测肾细胞凋亡。结果 B组和C组48 h血清BUN、Scr、MDA表达高于A组,但C组较B组显著降低(P<0.05);B组48 h血清SOD、GSH-Px表达较A组显著降低,C组SOD、GSH-Px表达显著高于B组(P<0.05),但仍低于A组;C组相同时间段病理改变较B组显著减轻,但仍重于A组;造模后48 h C组细胞凋亡较B组显著减轻(P<0.05),但仍重于A组。结论氧化应激和细胞凋亡可能参与大鼠CIN的发生发展,而羟苯磺酸钙可能通过减轻CIN大鼠氧化应激及细胞凋亡发挥保护作用。
关键词(KeyWords): 对比剂肾病;氧化应激;细胞凋亡;羟苯磺酸钙
基金项目(Foundation): 青岛医疗卫生优秀人才培养项目(青卫科教字【2014】8号)
作者(Author): 于芬芬,季文萱,单文红,孙艳,刘桂美,黄俊彦
参考文献(References):
- [1]Mohammed NM,Mahfouz A,Achkar K,et al.Contrast-induced Nephropathy.Heart Views,2013,14:106-116.
- [2]Golshahi J,Nasri H,Gharipour M.Contrast-induced nephropathy;A literature review.J Nephropathol,2014,3:51-56.
- [3]Buyuklu M,Kandemir FM,Ozkaraca M,et al.Protective effect of curcumin against contrast induced nephropathy in rat kidney:what is happening to oxidative stress,inflammation,autophagy and apoptosis?Eur Rev Med Pharmacol Sci,2014,18:461-470.
- [4]Ari E,Kedrah AE,Alahdab Y,et al.Antioxidant and renoprotective effects of paricalcitol on experimental contrastinduced nephropathy model.Br J Radiol,2012,85:1038-1043.
- [5]Kongkham S,Sriwong S,Tasanarong A.Protective effect of alpha tocopherol on contrast-induced nephropathy in rats.Nefrologia,2013,33:116-123.
- [6]Wu CT,Weng TI,Chen LP,et al.Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografininduced renal tubular cell injury.Toxicol Appl Pharmacol,2013,266:167-175.
- [7]谢泉琨,刘晓城.羟苯磺酸钙对2型糖尿病模型大鼠肾脏氧化应激的影响.中国药房,2004,15:721-723.
- [8]唐露,魏日胞,耿文佳,等.对比剂肾病发病机制及干预措施的研究进展.中华临床医师杂志(电子版),2013,7:3062-3064.
- [9]Heyman SN,Rosen S,Khamaisi M,et al.Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy.Investig Radiol,2010,45:188-195.
- [10]Zhu SY,Dong Y,Tu J,et al.Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose.Pharmacogn Mag,2014,10(Suppl1):S92-S99.
- [11]Garay RP,Hannaert P,Chiavaroli C.Calcium dobesilate in the treatment of diabetic retinopathy.Treat Endocrinol,2005,4:221-232.
- [12]Javadzadeh A,Ghorbanihaghjo A,Adl FH,et al.Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy.Mol Vis,2013,19:62-68.
- [13]Alda O,Valero MS,Pereboom D,et al.In vitro effect of calcium dobesilate on oxidative/inflammatory stress in human varicose veins.Phlebology,2011,26:332-337.
- [14]Cerrahoglu M,Taner Kurdal A,Iskesen I,et al.Calcium dobesilate reduces oxidative stress in cardiac surgery.J Cardiovasc Surg(Torino),2009,50:695-701.
- [15]高美娟,刘明,李波,等.羟苯磺酸钙对早期糖尿病肾病大鼠肾脏的保护作用.药学学报,2009,44:126-133.
- [16]Zhang X.Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1.Exp Ther Med,2013,5:295-299.
- [17]Jafarey M,Changizi Ashtiyani S,Najafi H.Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats.Iran J Kidney Dis,2014,8:46-52.