Regulatory Effect Of Qiteng Xiaozhuo Granule On Complement Cascade C1/C3/C5AR1 Signal Pathway In Rats With Chronic Glomerulonephritis

Objective Based on the regulation of complement cascade C1/C3/C5AR1 signal pathway,to explore the molecular mechanism of Qiteng Xiaozhuo granule in the treatment of chronic glomerulonephritis in(CGN)rats,and to provide ideas for finding new therapeutic targets for the treatment of chronic glomerulonephritis.Method A total of 72 SPF male SD rats were used.After one week of adaptive feeding,choose 10 rats as the normal group randomly,and the other rats were injected with adriamycin twice into the tail vein to establish the CGN rat model.Rats with 24-hour urinary protein content > 50mg/kg were randomly divided into model group,Qiteng Xiaozhuo granule group(21.6,10.8,5.4 g/kg)and positive drug Huangkui capsule group(1.0 g/kg).The rats were given corresponding doses of drugs or corresponding solvents for 30 days.After the last administration,the 24-hour urinary protein content was detected again,and the changes of 24-hour urinary protein content in each group were compared.The renal index and the contents of blood urea nitrogen(BUN),serum creatinine(Scr),cystatin C(Cys-C)and retinol binding protein(RBP)in serum were measured.Renal cortical tissue histomorphology was observed by HE staining,toluidine blue staining,Swiss Giemsa staining,Masson staining and hexaamine silver staining.Identification of leukocyte recruitment ability of rat renal cortical tissue by Transwell cell migration test.The expression levels of macrophage markers CD11 b,CD68 and CD80 were detected by immunofluorescence.The expressions of C1,C2,C3,C5 and C5AR1 m RNA in renal cortical cortical tissue of rats in each group were detected by RT-q PCR.The expression levels of C1,C2,C3,C5 and C5AR1 proteins were detected by Western blot and immunohistochemistry.Result Compared with the model group,Qiteng Xiaozhuo granule group and Huangkui capsule group could significantly improve the range of activity and food intake edema of rats,alleviate the weight loss of rats,and significantly reduce the content of 24-hour urinary protein in rats.Qiteng Xiaozhuo granule high and middle dose groups(21.6 g/kg,10.8 g/kg)and Huangkui capsule group could significantly reduce the contents of blood urea nitrogen,serum creatinine,cystatin C and retinol binding protein in serum,and improve the swelling of ren al cortical tissue in rats.Renal cortical tissue histopathological examination showed that Qiteng Xiaozhuo granule group and Huangkui capsule group could significantly improve glomerular atrophy,renal fibrous tissue hyperplasia,inflammatory cell infiltration,mast cells and neutrophils and other inflammatory cells,Improve the recruitment ability of renal cortical tissue lysate to leukocytes,and significantly reduce the expression levels of CD11 b,CD68 and CD80 in renal cortical tissue.Qiteng Xiaozhuo granule in high and middle dose groups(21.6 g/kg,10.8 g/kg)could significant ly reduce the protein expression levels of C1,C2,C3,C5,C5AR1 m RNA and C1,C2,C3,C5,C5AR1 in renal cortical tissue of CGN rats.Conclusion Qiteng Xiaozhuo granule has a therapeutic effect on chronic glomerulonephritis,and its mechanism may be related to the regulation of complement cascade C1/C3/C5AR1 signal pathway.