虾青素对低渗性对比剂诱导的大鼠急性肾损伤的保护作用  

Effect of astaxanthin intervention on contrast-induced acute kidney injury in experimental rats

作　　者：陈静[1] 李文华[1] 刘娜娜[1] 余亚仁 郑迪[1] 

机构地区：[1]江苏徐州医学院附属医院心内科,徐州221000

出　　处：《中华肾脏病杂志》2015年第8期604-609,共6页Chinese Journal of Nephrology

基　　金：江苏省六大人才高峰项目（2014-YY-007）

摘　　要：目的 研究虾青素（astaxanthin,AST）对低渗性非离子型对比剂碘海醇造成的大鼠急性肾损伤模型的保护作用其及机制.方法 SD大鼠被随机分为5组：对照组;虾青素对照组（100 mg/kg虾青素）;模型组;低剂量治疗组（50 mg/kg虾青素）;高剂量治疗组（100 mg/kg虾青素）;每组6只.虾青素对照组、低剂量治疗组、高剂量治疗组大鼠连续虾青素灌胃10d,其他组大鼠给予等体积溶剂灌胃.于实验第8天,除对照组及虾青素对照组外其余大鼠经股静脉注射吲哚美辛、左旋硝基精氨酸甲酯（NG-Nitro-L-arginine Methyl Ester,L-NAME）、碘海醇,建立对比剂急性肾损伤模型.注射碘海醇72 h后检测大鼠血清肌酐（Scr）、尿素氮（BUN）水平;HE染色观察肾组织病理改变;氧化应激试剂盒法检测肾组织丙二醛（MDA）含量,总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽（GSH）和过氧化氢酶（CAT）活性;Western印迹法检测肾组织B细胞淋巴瘤/白血病-2蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱天冬氨酸蛋白酶3 p17亚基（Caspase3 p17）的表达.结果 与对照组相比,模型组Scr、BUN水平明显升高;虾青素治疗组明显降低（均P＜0.01）.HE染色可见模型组肾小管损伤严重,髓质充血,肾小管结构破坏,上皮细胞刷状缘脱落、空泡变性、细胞坏死及蛋白质沉积.虾青素治疗组大鼠肾脏上述改变减轻,肾损伤评分减低（P＜0.05）;与对照组相比,模型组肾组织T-SOD、GPx、GSH活性下降,MDA含量增加（均P＜0.05）,虾青素治疗组大鼠上述指标明显改善（均P＜ 0.05）.Western印迹结果显示,与对照组相比,模型组大鼠肾组织Bax、Caspase-3 p17表达上调,Bcl-2表达下调;虾青素治疗组上述指标有明显改善（均P＜0.05）.结论 碘海醇导致肾组织氧化应激增加,激活Caspase-3信号通路,上调Bax表达,下调Bcl-2表达,导致细胞凋亡.虾青素通过抑制氧Objective To explore the protective effect and mechanism of astaxanthin （AST） on the acute kidney injury induced by iohexol in rats.Method Thirty rats were randomly divided into five groups：control group （Ctrl）;iohexol group （CM）;astaxanthin group （AST,100 mg/kg）,low astaxanthin dose group （LAST＋CM,50 mg/kg） and high astaxanthin dose group （HAST＋CM,100 mg/kg）,6 in each group.The rats in AST,LAST＋CM,HAST＋CM groups were administrated with AST by oral gavages using an intubation needle for 10 consecutive days.The rats in Ctrl and CM groups rats in Ctrl,CM groups were given with dissolvant instead in equal volume.Except for the Ctrl and AST groups,on day 8,rats were given indomethacin,L-NAME and iohexol in their femoral vein under chloral hydrate anesthesia to build a contrast induced-nephropathy （CIN） model.At the end of the experiment （72 h after CIN induction）,all rats were sacrificed.The Scr level,BUN level,renal histology,renal tissue activities in superoxide dismutase （SOD）,catalase （CAT）,glutathione peroxidase （GPx）,Glutathione （GSH） and level of malondialdehyde （MDA） were performed.Apoptosis of renal cells was detected by Bcl-2,Bax and Caspase-3 p17 with Western blot.Results Compared with Ctrl group,the levels of Scr,BUN were significantly increased in CM group （all P 〈 0.01）;while compared with CM group,the indicators were decreased in treatment groups （P 〈 0.01）.Renal tubular structure damage,medulla congestion,loss of brush border,vacuolar degeneration,apoptosis and proteinaceous casts were observed in the CM group,and the renal injury scores were higher compared with Ctrl group （P 〈 0.05）,however,administrated with AST could significantly improve the changes （P 〈 0.05）.Oxidative stress indicators showed that MDA level were increased while SOD,GPx,GSH activities were significantly decreased at CM group （all P 〈 0.05）,and the indicators above were ameliorated in treatment groups （all P 〈 0.05）.Western blot show

关 键 词：肾小管坏死 急性 氧化性应激 细胞凋亡 虾青素 

分 类 号：R692[医药卫生—泌尿科学]