Exploring the Effect of Astragaloside Ⅳ on the Immune Function of Systemic Lupus Erythematosus Mouse Model Based on NF-κB/NLRP3 Inflammasome
Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus(SLE)mice.Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups:model group,Prednisone group,astragaloside Ⅳ group,astragaloside Ⅳ+CHPG[nuclear factor KappaB(NF-κB)pathway activator]group and astragaloside Ⅳ+Nigerian[NOD-like receptor family pyrin domain containing protein 3(NLRP3)activator]group,with eight mice in each group.Eight female MRL/MpJ mice were used as normal group.During the administration,the body mass was weighted.After administration,the spleen,thymus and kidney were weighted,and the organ index was calculated.The 24-hour urinary protein level in urine samples,the biochemical indexes of creatinine(SCr),blood urea nitrogen(BUN),autoantibodies[antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody,anti-snRNP/Sm antibody]and inflammatory mediators[interleukin(IL)-1β,IL-18]in blood samples were detected.The pathological damage of renal tissue was observed by hematoxylin-eosin(HE)staining,and the fibrosis of renal tissue was observed by Masson staining.The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot.Results Compared with the model group,the body mass of mice in prednisone group and astragaloside Ⅳ group increased,the spleen index,thymus index and kidney index were decreased,the serum levels of ANA antibody,anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased,the levels of SCr,BUN and 24-hour urine protein were decreased,the levels of IL-1 βand IL-18 wrere decreased,the ratios of p-p65/p65,p-IKBα/IKBα,cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased(all P＜0.05),and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated,there being no significant difference between the two administration groups(P＞0.05).NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent.Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice,reduce renal injury and inflammatory response,and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.
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