甲基强的松龙通过NF-κB途径减轻狼疮易感MRL/lpr小鼠肾脏中脂多糖诱导的 fractalkine 表达。
Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.
作者信息
You Yanwu, Qin Yueqiu, Lin Xu, Yang Fafen, Li Jun, Sooranna Suren R, Pinhu Liao
机构信息
Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi Zhuang Autonomous Region, China.
Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi Zhuang Autonomous Region, China.
出版信息
BMC Nephrol. 2015 Aug 27;16:148. doi: 10.1186/s12882-015-0145-y.
BACKGROUND
Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis. It is known to be upregulated by lipopolysaccharide (LPS) as a stimulus in vivo. MRL/lpr mice have been used as an in vivo model to study lupus nephritis. Methylprednisolone (MP) is used widely in the clinical treatment of progressive glomerular diseases such as lupus nephritis. The aim of this study is to explore the mechanism of LPS induced FKN expression and to determine whether other molecular mechanisms contribute to the signaling pathway of MP action in MRL/lpr mice.
METHODS
Forty-eight female MRL/lpr mice at 12 weeks of age were randomly distributed into six groups. Each group received various treatments for 8 weeks by receiving twice weekly intraperitoneal injections of (1) MP (MP-treated mice), of (2) SC-514 (SC-514-induced mice), of (3) normal saline and a single injection of LPS (LPS-induced mice), of (4) MP and a single injection of LPS (LPS + MP mice), of (5) SC-514 and a single injection of LPS (LPS + SC mice) and of (6) normal saline (control mice). One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.
RESULTS
The expression of FKN and NF-kappaB p65 mRNA was detected by qPCR. The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively. The expression of FKN in the kidney of LPS induced mice was significantly increased and this was mediated by increased expression of NF-κB p65 and an increase in NF-kappaB phospho-p65. MP reduced proteinuria and ameliorated the renal damage in MRL/lpr mice. MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.
CONCLUSIONS
The results indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice through the NF-kappaB pathway.
背景
趋化因子（FKN）参与人类狼疮性肾炎的发生和发展。已知其在体内受脂多糖（LPS）刺激而上调。MRL/lpr小鼠已被用作研究狼疮性肾炎的体内模型。甲基强的松龙（MP）广泛用于狼疮性肾炎等进行性肾小球疾病的临床治疗。本研究旨在探讨LPS诱导FKN表达的机制，并确定是否有其他分子机制参与MP在MRL/lpr小鼠中的信号传导途径。
方法
将48只12周龄雌性MRL/lpr小鼠随机分为6组。每组通过每周两次腹腔注射接受各种治疗8周，分别为：（1）MP（MP治疗组小鼠），（2）SC-514（SC-514诱导组小鼠），（3）生理盐水和单次注射LPS（LPS诱导组小鼠），（4）MP和单次注射LPS（LPS+MP组小鼠），（5）SC-514和单次注射LPS（LPS+SC组小鼠），（6）生理盐水（对照组小鼠）。采用单因素方差分析进行数据分析，P值<0.05被认为具有统计学意义。
结果
通过qPCR检测FKN和NF-κB p65 mRNA的表达。分别通过免疫组织化学和蛋白质印迹法检测FKN蛋白的表达和NF-κB p65的激活。LPS诱导组小鼠肾脏中FKN的表达显著增加，这是由NF-κB p65表达增加和NF-κB磷酸化p65增加介导的。MP降低了MRL/lpr小鼠的蛋白尿并改善了肾损伤。MP以及NF-κB抑制剂SC-514抑制了LPS诱导的FKN表达增加和NF-κB的激活。
结论
结果表明，MP通过NF-κB途径减弱LPS诱导的MRL/lpr小鼠肾脏中FKN的表达。
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