光甘草定对大鼠对比剂急性肾损伤的保护作用及其主要机制研究Protective Effects and Main Mechanisms of Glabridin on Rats with Contrast-induced Nephropathy
刘巨旗,朱艺欣
摘要(Abstract):
目的观察光甘草定对大鼠对比剂急性肾损伤的保护作用及其主要机制。方法将50只SD大鼠随机分为空白组、模型组、光甘草定高剂量组、中剂量组及低剂量组。采用优维显碘普罗胺(10 mg/kg)尾静脉注射法对除空白组外其他各组大鼠进行造模,造模后,光甘草定高剂量组、中剂量组及低剂量组大鼠分别灌胃给予200、100、50 mg/kg的光甘草定,空白组及模型组则给予等量生理盐水,各组均连续给药3 d。末次给药24 h后,采用尾静脉取血法取各组大鼠静脉血,检测其中血肌酐(Scr)及尿素氮(BUN)等肾功能指标含量。取血后取各组大鼠双侧肾,观察左侧肾病理组织学变化;将右侧肾脏分成4份,采用荧光免疫组化法观察其中血红素加氧酶(HO-1)、过氧化氢酶(CAT)、8-羟基脱氧鸟苷(8-OHDG)及髓过氧化物酶(MPO)的表达情况,并统计上述蛋白的相对表达量。结果与模型组比,空白组、光甘草定高剂量组、中剂量组及低剂量组大鼠Scr及BUN均明显降低(P <0.05)。HE染色结果显示,高剂量组、中剂量组及低剂量组大鼠呈现不同程度肾小球内皮细胞变性、肾小管结构破坏及肾间质炎性细胞浸润,但程度均不及模型组。荧光免疫组化染色中,光甘草定高剂量组、中剂量组及低剂量组大鼠肾组织中HO-1及CAT阳性表达情况明确强于模型组,而8-OHDG及MPO阳性表达情况明确弱于模型组。半定量分析结果表明,与模型组比较,高剂量组、中剂量组及低剂量组HO-1及CAT相对表达量均明显增高,而8-OHDG及MPO相对表达量均明显降低(P <0.05)。结论光甘草定可有效改善对比剂急性肾损伤大鼠肾脏功能,其主要机制可能与该化合物的抗氧化活性有关。
关键词(KeyWords): 光甘草定;对比剂急性肾损伤;保护作用;主要机制
基金项目(Foundation): 陕西省中医药管理局中医药科研课题(15-LC064)
作者(Author): 刘巨旗,朱艺欣
参考文献(References):
- [1] Habib M,Hillis A,Hammad A. N-acetylcysteine and/or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients undergoing elective cardiac catheterization:The NAPCIN trial; A single-center, prospective,randomized trial[J]. Saudi J Kid ney Dis Transpl,2016,27(1):55-61.
- [2]熊丹,瞿红霞,李良,等.对比剂肾病的研究进展[J].心脏杂志,2016,28(1):110-113.
- [3] Celik O,Ozturk D,Akin F,et al. Association between contrast media volume-glomerular filtration rate ratio and contrast-induced acute kidney injury after primary percutaneous coronary intervention[J]. Angiology,2015,66(6):519-524.
- [4]鲍文芳,方路,施映枫,等.造影剂肾病的研究进展[J].中国中西医结合肾病杂志,2016,17(3):277-280.
- [5]冯倩茹,叶柳青,刘园园,等.鹅掌楸苷和光甘草定协同抗氧化作用研究[J].天津中医药,2016,33(10):624-628.
- [6]孙敬方.动物实验方法学[M].北京:人民卫生出版社,2001:198-201.
- [7] Liu T,Fang Y,Liu S,et al. Limb ischemic pre conditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3β[J]. Free Radic Biol Med,2015,81:170-182.
- [8] Kanda T,Fukusato T,Matsuda M,et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction:evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy[J]. Radiology,2015,276(1):228-232.
- [9] He J,Wang Q,Ma X,et al. Dual-energy CT angiography of abdomen with routine concentration contrast agent in comparison with conventional single-energy CT with high concentration contrast agent[J]. Eur J Radiol,2015,84(2):221-227.
- [10] Fu H,Li G,Liu C,et al. Probucol prevents atrial remodeling by inhibiting oxidative stress and TNF-α/NF-κB/TGF-βsignal transduction pathway in alloxan-induced diabetic rabbits[J]. J Cardiovasc Electrophysiol,2015,26(2):211-222.
- [11] Su X,Wang Y,Zhou G,et al. Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting oxidative stress, extracellular matrix protein accumulation and cytokine production[J]. Clin Exp Pharmacol Physiol,2014,41(1):73-80.
- [12] Ueno Y,Yamashiro K,Tanaka Y,et al. Rosuvastatin may stabilize atherosclerotic aortic plaque:transesophageal echocardiographic study in the EPISTEME trial[J]. Atherosclerosis,2015,239(2):476-482.
- [13]彭佳,谭波宇,宁宁,等.造影剂肾病发病机制、危险因素及防治的研究进展[J].中国医药导报,2017,14(3):43-46.
- [14] Heyman SN,Rosen S,Khamaisi M,et al. Reactive oxygen species and thepathogenesis of radiocontrast-induced nephropathy[J]. Invest Radiol,2010,45(4):188-195.
- [15]王淦娴,王怡,丁俊丽,等.光甘草定通过p38/MAPK通路调控动脉粥样硬化模型兔动脉MLCK表达[J].安徽医科大学学报,2017,52(3):309-313.
- [16]赵焱,卢祖能.光甘草定对MPTP致帕金森病小鼠海马区ERK信号通路的影响[J].中华医学杂志,2017,97(26):2050-2054.
- [17]龚学忠,邱安东,段怡汝,等.制大黄-川芎药对对CIN大鼠肾组织Nrf2/HO-1信号通路的影响[J].上海中医药大学学报,2017,31(6):58-61.
- [18]于德玲,王昌留.过氧化氢酶的研究进展[J].中国组织化学与细胞化学杂志,2016,25(2):189-194.
- [19]朴恩谊,徐立红. 8-OHdG在医学领域的应用与研究进展[J].中国细胞生物学学报,2012,34(5):493-499.
- [20]李安宁,吴越,姚振,等.基于髓过氧化物酶的分子探针成像研究进展[J].放射学实践,2017,32(9):984-989.