鼠尾草酸对庆大霉素诱导急性肾损伤的保护作用  

Protective effect of carnosic acid on gentamycin-induced acute kidney injury

作　　者：曹静[1] 何苗 罗颂[1] 刘辉[1] CAO Jing;HE Miao;LUO Song;LIU Hui(Department of Pharmacy,Hu′nan Children Hospital,Changsha 410007,China)

机构地区：[1]湖南省儿童医院药学部,长沙410007

出　　处：《西北药学杂志》2021年第1期61-65,共5页Northwest Pharmaceutical Journal

摘　　要：目的研究鼠尾草酸对庆大霉素(GM)诱导急性肾损伤的作用及其可能的机制。方法将SD大鼠随机分为对照组、模型组、阳性对照组以及鼠尾草酸低、中、高剂量组。鼠尾草酸给药组和阳性对照组分别用不同剂量的鼠尾草酸或肾衰宁灌胃7 d,同时合并GM腹腔给药,模型组单独使用GM处理7 d。检测血清中肌酐(SCr)和血尿素氮(BUN)的水平;HE染色检测肾脏组织的病理改变情况;免疫组化检测各组大鼠肾脏组织中肾损伤分子-1(KIM-1)的表达;检测各组大鼠肾组织中丙二醛(MDA)和过氧化氢(H2O2)的含量,诱导型一氧化氮合酶(iNOS)和超氧化物歧化酶(SOD)的酶活力;酶联免疫吸附测定法检测肾脏组织中单核细胞趋化蛋白1(MCP-1)和肿瘤坏死因子α(TNF-α)的含量;Western Blot法测定肾脏组织中p66shc和p-p66shc的蛋白表达。结果与对照组比较,模型组大鼠血清SCr和BUN水平上升,MDA、H2O2含量和iNOS酶活力明显上升,SOD酶活力下降;与模型组比较,鼠尾草酸中、高剂量组可降低这些改变。与对照组相比,肾脏组织中MCP-1、TNF-α、KIM-1以及p-p66shc含量明显上升;与模型组比较,鼠尾草酸中、高剂量可降低GM诱导肾脏组织中MCP-1、TNF-α、KIM-1以及p-p66shc的含量。结论鼠尾草酸能显著降低GM诱导的急性肾损伤,其机制与抑制p66shc介导的氧化应激有关。Objective To investigate the effect of carnosic acid on gentamycin(GM)-induced acute kidney injury and to explore the possible mechanism.Methods SD rats were randomly divided into 6 groups:control group,model group,positive control group,carnosic acid low,middle and high dose groups.The rats in carnosic acid group and positive control group were treated with various doses of carnosic acid and Shenshuaining for 7 d,respectively,and combined with GM(i.p.).The rats in the test group were treated with different doses of carnosic acid combined with GM(i.p.)for 7 d,and the rats in the model group were administered with GM(i.p.)for 7 d.The levels of renal function related indicators,such as serum creatinine(SCr)and blood urea nitrogen(BUN)were detected.H&E staining was used to detect the pathological changes of kidney tissue.Immunohistochemical was used to detect the level of kidney injury molecule-1(KIM-1).The contents of malondialdehyde(MDA),hydrogen peroxide(H2O2)and enzyme activity of superoxide dismutase(SOD)and inducible nitric oxide(iNOS)in kidney tissue were determined.The enzyme linked immunosorbent assay kit was used to measure the content of monocyte chemotactic protein 1(MCP-1)and tumor necrosis factorα(TNF-α)in the kidney tissue.The level of protein expression of p66shc and p-p66shc was detected by using Western Blot method.Results Compared with the control group,the levels of SCr and BUN in serum were increased,and the contents of MDA,H 2O 2 and activity of iNOS in kidney tissue were increased in model group,but the enzyme activity of SOD was decreased.Compared with the model group,the middle and high dose of salicylic acid was able to inhibit these effects.Compared with control group,the contents of MCP-1,TNF-α,KIM-1 and p-p66shc were increased in kidney tissue of model group.Compared with the model group,the up-regulation of MCP-1,TNF-a,KIM-1 and p-p66shc by GM were inhibited following the treatment with middle and high dose of salicylic acid.Conclusion Carnosic acid can significantly reduce GM induce

关 键 词：鼠尾草酸 急性肾损伤 P66SHC 庆大霉素 

分 类 号：R965[医药卫生—药理学]