复方生地合剂对MRL/lpr狼疮小鼠TLR-NF-κB信号通路的调节作用

Regulation of compound Shengdi mixture on tlr-nf-κB signaling pathway in MRL/lpr lupus mice

目的:探讨复方生地合剂对MRL/lpr狼疮小鼠Toll样受体(toll like receptors,TLRs)-核因子-κB(nuclear factorκB,NF-κB)信号通路的调节作用。方法:采用随机数字表法将MRL/lpr狼疮小鼠随机分组为模型组、中药组、西药组,另以C57BL/6小鼠作为空白组每组10只,均为12周龄雌性小鼠。中药组给予复方生地合剂灌胃治疗,西药组给予强的松悬液灌胃治疗,对照组和模型组以生理盐水灌胃治疗。8周后取外周血和脾脏分别检测外周血抗双链DNA抗体(Anti-double-stranded DNA antibody,dsDNA抗体)、干扰素-α(Interferon-α,IFN-α)和肿瘤坏死因子(tumor necrosis factor-α,TNF-α)水平、脾组织中TLR7/9,髓样分化因子88(myeloid differentiation primary-response gene 88,MyD88),NF-κB的基因表达以及TLR7、MyD88、NF-κB的蛋白表达。结果:模型组外周血dsDNA抗体、TNF-α和IFN-α水平高于空白组,中药组dsDNA抗体、TNF-α和IFN-α水平均低于模型组;模型组脾组织的TLR7、TLR9、MyD88和NF-κB的mRNA和蛋白表达都高于空白组mRNA和蛋白表达水平;中药组脾组织TLR7、TLR9、MyD88和NF-κB的mRNA以及TLR7、MyD88和NF-κB p65的蛋白表达水平都低于模型组mRNA和蛋白表达水。结论:复方生地合剂可以降低MRL/lpr狼疮小鼠外周血dsDNA水平,可能通过下调MRL/lpr狼疮小鼠TLR-MyD88-NF-κB通路发挥作用。

Objective:To investigate the regulation of compound Shengdi Mixture on TLR-NF-κB signaling pathway in MRL/lpr mice.Methods:MRL/lpr mice were randomly divided into model group,Chinese medicine group and western medicine group.C57BL/6 mice were used as normal control group.Ten mice in each group were female mice of 12 weeks old.The Chinese medicine group was given the compound Shengdi mixture for intragastric administration,and the western medicine group was given the treatment with prednisone.The blank group and the model group were replaced with physiological saline.After 8 weeks,peripheral blood and spleen were taken.The levels of dsDNA,IFN-αand TNF-αin peripheral blood,TLR7/9,MyD88,NF-κB gene expression and TLR7,MyD88 and NF-κB proteins in spleen were detected.Results:1The levels of dsDNA antibody,TNF-αand IFN-αin the peripheral blood of the model group were higher than those in the blank group.The dsDNA antibody,TNF-αand IFN-αlevels in the Chinese medicine group were lower than those in the model group.The expressions of TLR7 mRNA,TLR9 mRNA,MyD88 mRNA and NF-κB mRNA and TLR7,MyD88 and NF-κB p65 in spleen of model group were higher than those in blank group.The expression levels of TLR7 mRNA,TLR9 mRNA,MyD88 mRNA and NF-κB mRNA and TLR7,MyD88 and NF-κB p65 in spleen tissues of Chinese medicine group were lower than those in model group.Conclusion:Compound Shengdi Mixture can reduce the dsDNA level in peripheral blood of MRL/lpr lupus mice,possibly by down-regulating the TLR-MyD88-NF-κB pathway in MRL/lpr lupus mice.