金黄霉素A对脂多糖诱导小鼠急性肾脏炎症的作用及其可能机制

Effects of Chrysomycin A on Lipopolysaccharide-Induced Acute Renal Inflammation in Mice and Its Possible Mechanism

目的研究金黄霉素A(chrysomycin A,Chr-A)对脂多糖(lipopolysaccharides,LPS)诱导小鼠急性肾脏炎症反应的作用及机制。方法BALB/c小鼠随机分为正常对照组、LPS模型组、Chr-A 3 mg·kg^(-1)和10 mg·kg^(-1)给药组。Chr-A连续给药7 d后,LPS模型组和各Chr-A给药组腹腔注射5 mg·kg^(-1)的LPS,6 h后取血清和肾脏组织进行检测。检测血清尿素氮(BUN)评价肾功能;ELISA法检测肾组织中白细胞介素1β(Interleukin-1β,IL-1β)、白细胞介素6(Interleukin-6,IL-6)、单核细胞趋化蛋白1(monocyte chemoattractant protein,MCP-1)以及肿瘤坏死因子α(tumor necrosis factorα,TNF-α)水平;Western blot检测炎症相关蛋白环氧合酶2(cyclooxygenase 2,COX2)、NLRP3炎性小体及嘌呤能离子通道型受体7(P2X7)的表达。结果Chr-A剂量依赖性降低LPS刺激引起的血清BUN水平升高;此外,Chr-A剂量依赖性降低LPS刺激引起的肾脏组织中IL-β,IL-6,TNF-α,MCP-1及COX2炎症因子的升高;进一步研究发现,Chr-A显著下调炎症通路相关蛋白P2X7和NLRP3的表达。结论Chr-A具有抗LPS诱导的小鼠急性肾脏炎症反应作用,机制可能与下调炎症蛋白P2X7和NLRP3相关。

OBJECTIVE To investigate the effects and possible mechanisms of chrysomycin A(Chr-A)on lipopolysaccharide(LPS)-induced acute renal inflammation in mice.METHODS BALB/c mice were randomly divided into control group,LPS model group and Chr-A 3,10 mg·kg^(-1) treatment groups.After 7 d of Chr-A administration,the mice in LPS model group and Chr-A treatment groups were injected with 5 mg·kg^(-1) LPS intraperitoneally and renal tissues were obtained for the following detection after 6h of LPS injection on the 7^(th) day.The levels of BUN(urea nitrogen)in the serum was detected to assess the kidney function;the levels of IL-1β,IL-6,TNF-αand MCP-1 in renal tissues were measured by ELISA;the expression of inflammatory protein,including COX2,NLRP3 and P2X7 were detected by Western blot.RESULTS Chr-A dose dependently decreased the level of serum urea nitrogen increased by LPS stimulation.In addition,Chr-A dose dependently decreased the inflammatory factors including IL-1β,IL-6,TNF-α,MCP-1 and COX2 in the renal tissues stimulated by LPS.Further studies found that Chr-A significantly down-regulated the expression of inflammatory pathway related proteins P2X7 and NLRP3.CONCLUSION Chr-A has acute renal inflammatory response,and the mechanism may be related to the down regulation of inflammatory proteins P2X7 and NLRP3.