山东医药2017，Vol.57Issue(30)：10-13,4.DOI:10.3969/j.issn.1002-266X.2017.30.003
积雪草酸预处理对脓毒症小鼠急性肾损伤的影响及机制
Effects of pretreatment of asiatic acid on acute renal injury of mice with sepsis
摘要
Abstract
Objective To investigate the protective effects of pretreatment of asiatic acid (AA) on acute renal injury of mice with sepsis.Methods Twenty-four male BALB/c mice were randomly divided into the blank control group, lipopolysaccharide (LPS) group, low-dose AA group, and high-dose AA group with 6 mice in each.Mice in the low-dose AA group and high-dose AA group were administered 10 and 30 mg/kg AA for 3 consecutive days, meanwhile, mice in the blank control and LPS group were intragastrically administered equal volume of 0.5% sodium carboxyl methyl cellulose (CMC-Na).At 2 h after the last administration, mice in the blank control group were intraperitoneally injected with PBS, while mice in the other three groups were injected with 10 mg/kg LPS to make the sepsis models.After 4-hour LPS injection on day 3, the level of serum urea nitrogen (BUN) was measured by diacetylmonoxime colorimetric assay.The pathological change of kidney was investigated by HE staining.The mRNA expression levels of cytokines (TNF-α, IL-1β and IL-6) and Notch signaling pathway-related genes (Notch1-4, Dll4, and Jag2) were measured by real-time PCR.Results Compared with the blank control group, the level of BUN in the LPS, low-dose and high-dose AA groups was higher.Meanwhile, the level of BUN in the low-dose AA and high-dose AA groups was lower than that of the LPS group (all P<0.05).The histological examination showed LPS treatment resulted in neutrophil infiltration, tubular necrosis and endothelial cell swelling.Against these changes, the low-dose and high-dose AA groups showed significantly alleviated neutrophil infiltration, endothelial cell swelling and pathological injury as compared with that of the LPS group.The mRNA levels of TNF-α, IL-1β, and IL-6 in the LPS group were higher than those of the blank control group (all P<0.05), at the same time, the mRNA levels of TNF-α, IL-1β, and IL-6 in the low-dose and high-dose AA groups were lower than those of the LPS group (all P<0.05).The mRNA levels of Notch related genes including Notch1, Notch2, Notch3, Notch4, Dll 4 and Jag2 in the LPS group were lower than those of the blank control group (all P<0.05), meanwhile, the mRNA levels in the low-dose and high-dose AA groups were higher than those of the LPS group (all P<0.05).Conclusion AA pretreatment may significantly alleviate the acute renal injury of mice with sepsis by regulating Notch signaling pathway to develop anti-inflammatory effect.关键词
积雪草酸/肾脏/脂多糖/Notch信号通路/炎症因子/脓毒症/急性肾损伤Key words
asiatic acid/kidney/lipopolysaccharide/Notch signaling pathway/inflammation/sepsis/acute kidney injury分类
医药卫生引用本文复制引用
朱丽华,熊御云,夏琳,芮棵,阴晴..积雪草酸预处理对脓毒症小鼠急性肾损伤的影响及机制[J].山东医药,2017,57(30):10-13,4.基金项目
国家自然科学基金资助项目(81301657) （81301657）
江苏省自然科学基金资助项目(BK20130476). （BK20130476）
