基于肺-咽-肾轴构建紫癜性肾炎合并慢性咽炎疾病复合模型OA

Objective To construct and evaluate a novel disease complex model of Henoch-Schönlein purpura nephritis(HSPN)combined with chronic pharyngitis(CP)in rats,based on the"lung-pharynx-kidney"axis.Methods Thirty-six specific pathogen-free grade male Sprague-Dawley rats were divided into control,HSPN,and HSPN-CP groups using a random number table(12 mice in each group).A composite method involving gavage administration of bovine serum albumin,subcutaneous injection of carbon tetrachloride,and caudal vein administration of lipopolysaccharide was used to establish the HSPN model.The HSPN-CP group received repeated submucosal injections of Group A β-hemolytic streptococcus solution into the pharyngeal mucosa on the first,fourth,seventh,10th,13rd,and 16th days after the 12th week to induce CP.After the modeling period,changes in renal function were evaluated by measuring urine red blood cell count,24-hour urinary protein quantification,and serum biochemical indexes.The levels of inflammatory factors,including interleukin-4,interleukin-6,and tumor necrosis factor-α,were measured to evaluate the changes in inflammation.HE staining,immunofluorescence staining,and transmission electron microscopy(TEM)were used to evaluate the pathology,immunology,and ultrastructure of pharynx,lung,and kidney tissues of rats in each group.Results(1)Compared with the control group,the rats in the HSPN group exhibited typical renal injury characteristics,including significantly elevated levels of urinary protein,urine red blood cell count,serum blood urea nitrogen,serum creatinine,and inflammatory factors(P＜0.05).Renal histopathological examination revealed mesangial cell proliferation,matrix widening,and IgA immune complex deposition.(2)Compared with the HSPN group,the above-mentioned indicators of renal injury were significantly exacerbated in the HSPN-CP group.HE staining showed that the pathological damage of the kidneys in the HSPN-CP group was more serious;the pharyngeal tissues displayed epithelial necrosis and shedding with massive inflammatory cell infiltration;and lung tissues showed destruction of alveolar structure,interstitial thickening,and significant inflammatory infiltration.Immunofluorescence and TEM revealed that IgA deposition in the glomerular mesangial area of the HSPN-CP group was significantly increased,the fluorescence intensity was increased,the deposition range was wider,the electron dense deposition was more,and the foot process fusion was more serious.Conclusion This study successfully established a disease complex model of HSPN combined with CP.Persistent pharyngeal streptococcal infection can significantly aggravate the renal injury and systemic inflammatory response in HSPN rats,while also inducing pathological changes in the lungs.This study provides robust experimental evidence for the"lung-pharynx-kidney"axis and the role of mucosal immunity in the pathogenesis of HSPN.