The improvement of intestinal immune barrier function in immunoglobulin A nephropathy rats by Atractylolactone-Ⅲ nanoparticles
Objective To explore the effects of Atractylenolide-Ⅲ(AT-Ⅲ)on the intestinal immune barrier and kidney of rats with immunoglobulin A nephropathy(IgAN),and develop AT-Ⅲ nanoparticles to optimize its protective efficacy.Methods In this study,the zeolitic imidazolate framework(ZIF-8)loaded with AT-Ⅲ was used to prepare ZIF-8@AT-Ⅲnanoparticles.Morphological and structural characterization of the prepared samples was conducted using transmission electron microscopy and X-ray powder diffraction.48 rats were randomly divided into the normal control group,IgAN group,IgAN+AT-Ⅲ group,and IgAN+ZIF-8@AT-Ⅲ group.IgAN rats were treated with AT-Ⅲ and ZIF-8@AT-Ⅲ,and the detections of hepatic and renal function,glomerular IgA deposition,and intestinal immune barrier function were performed.Results The synthesis of ZIF-8@AT-Ⅲ nanoparticles with elevated drug loading,stability,and pH responsiveness had been successfully accomplished.The average particle size of ZIF-8@AT-Ⅲ nanoparticles was(70.62±1.07)nm,the Zeta potential was(-26.46±1.22)mV,the drug loading capacity was(19.2±1.3％),and the encapsulation efficiency was(64.0％±0.6％).Furthermore,rapid release was observed in a pH 5.5 environment,which was significantly higher than that in the pH 7.4 environment.Both AT-Ⅲ and ZIF-8@AT-Ⅲcould alleviate the destruction of intestinal wall structure and the infiltration of inflammatory cells,significantly downregulate the levels of(DAO)and(D-LA)in the serum.Moreover,there is a noteworthy upregulation in the expression of(ZO-1)and Claudin-5 in intestinal mucosal tissue,thereby substantially improving the immune barrier function and intestinal permeability in IgAN rats.This intervention also inhibited the deposition of IgA in renal glomeruli and alleviated kidney damage,and ZIF-8@AT-Ⅲ was more effective than AT-Ⅲ.Conclusion AT-Ⅲ alleviates IgAN in rats by improving intestinal immune barrier function and permeability.ZIF-8-loaded AT-Ⅲ serves as an excellent drug delivery system,enhancing the therapeutic efficacy of AT-Ⅲ in IgAN treatment.
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