机构地区:[1]三峡大学第三临床医学院葛洲坝集团中心医院,湖北宜昌443000
出 处:《中国实验方剂学杂志》2017年第17期177-182,共6页Chinese Journal of Experimental Traditional Medical Formulae
基 金:湖北省自然科学基金项目(2014CFC1147)
摘 要:目的:研究葛根素(Puerarin)对庆大霉素诱导急性肾损伤的影响作用及其机制。方法:利用庆大霉素损伤Wister大鼠肾组织构建急性肾损伤模型。分别设置未损伤空白组(空白组),急性肾损伤模型组(模型组),急性肾损伤后不同浓度葛根素处理组(分别皮下注射0.5,5,50 mg·kg^(-1)Puerarin)。苏木素-伊红(HE)染色观察各组大鼠肾组织形态学改变;检测各组大鼠肾组织中超氧化物歧化酶(SOD)活力,丙二醛(MDA),总抗氧化能力(TAOC),诱导型一氧化氮合酶(iNOS)含量;同时测定各组大鼠肾功能相关指标血肌酐(SCr),尿肌酐(UCr),血清尿素氮(SBUN)和尿尿素氮(UBUN)含量变化;酶联免疫吸附(ELISA)检测各组大鼠肾组织中单核细胞趋化蛋白-1(MCP-1),肿瘤坏死因子-α(TNF-α),受激活调节正常T细胞表达和分泌因子(RANTES),巨噬细胞炎症蛋白-2(MIP-2)等炎症蛋白的含量变化;蛋白免疫印迹法(Western blot)检测各组大鼠肾组织中肾损伤分子-1(KIM-1)表达变化。结果:与空白组比较,庆大霉素诱导急性肾损伤大鼠肾小管坏死评分上升,SCr,UCr,SBUN和UBUN含量上升,而SOD,TAOC活力下降,MDA含量,iNOS活力明显上升,MCP-1,TNF-α,RANTES,MIP-2含量及KIM-1蛋白表达明显上升(P<0.05);不同浓度葛根素组中,急性肾损伤大鼠肾小管坏死评分逐渐下降,SCr,UCr,SBUN和UBUN随之降低,SOD,TAOC活力上升,MDA含量,iNOS活力逐渐下降,MCP-1,TNF-α,RANTES,MIP-2含量及KIM-1蛋白表达逐渐下降(P<0.05)。结论:葛根素能够显著降低庆大霉素诱导急性肾损伤大鼠的肾小管坏死、提升肾组织功能和抗氧化能力、抑制炎症反应和KIM-1蛋白表达,从而减轻庆大霉素诱导的急性肾损伤。Objective: To study the effect and mechanism of Puerarin on gentamicin-induced acute kidney injury. Method: The acute kidney injury model was built with gentamicin in Wister rats and divided into the no injury control group (blank group), the acute kidney injury model group (model group), and different doses of Puerarin treatment groups ( subcutaneous injection of 0.5, 5, 50 mg·kg^-1 Puerarin). Hematoxylin-eosin (HE) staining was used to observe the morphological changes in renal tissues of rats in each group; superoxide dismutase (SOD) activity, malondialdehyde ( MDA), total antioxidant capacity (TAOC), inducible nitric oxide synthase (iNOS) contents in kidney tissues of rats were detected in each group. Meanwhile, the changes of serum creatinine (SCr) , urinary creatinine (UCr) , blood urea nitrogen (SBUN) and urea urea nitrogen (UBUN) levels were determined in all groups. Changes in monocyte chemoattractant protein-1 (MCP-1) , tumor necrosis factor alpha (TNF-α) and regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein-2 (MIP-2) and other inflammatory protein contents were tested by enzyme linked immunosorbent assay (ELISA). And changes in the kidney injury molecular-1 (KIM-1) expression in renal tissues were detected by Western blot. Result: Compared with the no injury control group, in the gentamicin- induced acute kidney injury group, renal tubular necrosis score were increased, SCr, UCr, SBUN and UBUN content increased, the activity of SOD, TAOC decreased, the content of MDA and iNOS activity significantly increased, and MCP-1, TNF-α, RANTES, MIP-2 contents and KIM-1 protein content increased significantly (P 〈0.05). In different concentrations of Puerarin groups, scores for renal tubular necrosis in rats with acute kidney injury were decreased gradually, SCr, UCr, SBUN and UBUN decreased, while SOD, TAOC activity increased, MDA content, and iNOS activity decreased, MCP-1,
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