摘要
目的:研究人参二醇组皂苷(PDS)和地塞米松(DEX)是否具有类似的减轻LPS诱导的小鼠急性肾损伤(AKI)的作用,并探讨它们的作用机制。方法:C57BL/6小鼠随机分为4组,除对照组腹腔注射生理盐水外,其余3组均经腹腔注射LPS 10 mg/kg,PDS组和DEX组小鼠在LPS注射前1 h分别经腹腔注射PDS(25.0 mg/kg)或DEX(2.5 mg/kg)。12 h后麻醉下取血和肾脏组织备生物化学与免疫印迹检测。结果:LPS组小鼠血尿素氮和肌酐含量显著高于对照组(P<0.01),而PDS组和DEX组则明显低于LPS组(P<0.05);PDS和DEX上调LPS处理的小鼠肾组织IκB蛋白的表达,抑制NF-κB信号通路的活化,进而减少TNF-α和IL-6的产生;PDS和DEX均能下调LPS处理的小鼠肾脏诱导型一氧化氮合酶(iNOS)的表达,上调肾组织锰过氧化物歧化酶的表达,减轻肾脏的氧化应激损伤。此外,PDS和DEX均明显上调LPS处理的小鼠肾脏组织细胞核糖皮质激素受体蛋白的含量。结论:人参二醇组皂苷具有与DEX相类似的减轻LPS诱导的小鼠AKI的作用,而且,它们的作用机制相似,但PDS的药效学是否也通过糖皮质受体介导还需进一步研究。
AIM： To investigate whether the panaxadiol saponins （PDS） anti dexamethasone .（ DEX ） have similar effects on lipopolysaceharide （LPS）-induced acute kidney injury （AKI）. METHODS： C57BL/6 mice were, randomly divided into 4 groups： the control mice received intraperitoneal injeetion of normal saline; in LPS group, the mice were subjected to intraperitoneal injection of LPS （ 10 mg/kg） ; in PDS ＋ LPS group and DEX ＋ LPS group, the mice were, injected intraperitoneally with PDS （25.0 mg/kg） and DEX（2.5 mg/kg） I h before LPS injection, respectively. The blood was collected from the hearts, and the kidneys were collected for the hiochemical and Western hlotting analysis 12 h after LPS injection. RESULTS： LPS induced AKI, evidenced hy markedly increased blood urea nitrogen （BUN） and creatinine （CREA） contents compared with control group （P 〈0.01 ）. However, serum contents of CREA and BUN obviously reduced in PDS ＋ LPS group and DEX ＋ LPS groups compared with I,PS group （ P 〈 0. 05）. Both PDS anti DEX decreased the production of TNF-α and II,-6 hy inhihiting renal NF-KB signaling activation. PDS anti DEX also down-regulated the expression of inducible nitric oxide synthase, up-regulated the expression of manganese superoxide dismulase and reduced oxidative slress in the kidneys of LPS-challenged mice. In addition, treatment with PDS and DEX significantly increased the nuclear glucoeorticoid receptor in the kidneys of LPS-treated mice. CONCLUSION： PDS and DEX have inhihitory effects on LPS-induced AKI mice. However, it is unclear whether PDS reduces LPS-induced AKI via direct action on glucocorticoid receptor.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2014年第5期864-869,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81170304)
