基于BAFF/APRIL调控Gd-IgA1生成探讨凉血退紫方治疗紫癜性肾炎血热证模型大鼠的机制研究OA

Objective To investigate the mechanism by which Liangxue Tuizi Formula(LXTZF)treats Henoch-Schönlein purpura nephritis(HSPN)with blood-heat syndrome in rats by regulating the B-cell activating factor(BAFF)/a proliferation-inducing ligand(APRIL)signaling pathway and inhibiting the production of galactose-deficient immunoglobulin A1(Gd-IgA1).Methods Sixty Wistar rats were randomly divided into control group(n=11)and modeling group(n=49).After modeling,the control group was reduced to 8 rats following sampling verification;the modeling group was then subdivided into a model group(n=8),prednisone group(5.4 mg/(kg·d),n=8),and low-dose LXTZF(LD,3.8 g/(kg·d),n=7),medium-dose LXTZF(LZ,7.5 g/(kg·d),n=8),and high-dose LXTZF(LG,15.0 g/(kg·d),n=8)groups.Interventions were administered continuously for 4 weeks.Drug efficacy was evaluated by measuring 24-hour urinary protein,urinary red blood cell counts,histopathological changes,and molecular biological parameters.Results The results of model validation demonstrated renal pathological damage in the modeling group,confirming the successful establishment of the animal model.Compared with control group,model rats showed significant increases in urinary protein,urinary red blood cell counts,serum IgA1,Gd-IgA1,BAFF,APRIL,and renal circulating immune complexes(CIC,P<0.001),together with marked renal pathological renal injury.After drug treatment,the prednisone,LZ and LG groups showed significant improvements in renal pathology(P<0.05,P<0.01,P<0.001).Notably,LZ and LG groups further downregulated the gene and protein expression levels of key molecules in the BAFF/APRIL signaling pathway,including BAFF,APRIL,and their receptors BAFF-R,BCMA,and TACI in renal tissue(P<0.05,P<0.01,P<0.001).Conclusions LXTZF may ameliorate cutaneous and renal injury in HSPN with blood-heat syndrome by suppressing BAFF/APRIL signaling,thereby reducing Gd-IgA1 production and CIC deposition.