基于"肠-肾轴"理论探讨肾必宁颗粒对IgA肾病大鼠的抗炎机制OA

Objective:To study the effects of Shenbining Granules on the inflammatory signaling pathway of spleen tyrosine kinase(Syk)and colonic pathology in IgA nephropathy(IgAN)rats based on the theory of'gut-kidney axis',and to explore the mechanism of Shenbining Granules in treating IgAN.Methods:A total of 42 male SD rats were randomly divided into control group,model group,prednisone group(12.5 mg/kg)and Shenbining Granules low-dose(20.5 g/kg)and high-dose(41.0 g/kg)groups.The IgAN rat model was established by intragastric administration of bovine serum albumin(BSA),subcutaneous injection of carbon tetrachloride(CCl4)and castor oil,tail vein injection of lipopolysaccharide(LPS).Starting from the 4th week of modeling,each group was given the corresponding dose of drug intragastric administration,and the control group and model group were given the same amount of distilled water.After 14 weeks of continuous intragastric administration,blood,urine,kidney and colon tissues were collected.The levels of 24 h urinary protein(24 h-UTP),urine red blood cell count(URBC),serum albumin(ALB),alanine aminotransferase(ALT),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of kidney tissue and colon.IgA deposition in mesangial region was observed by immunofluorescence.Serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)levels were detected by ELISA.Western Blot,Real-time PCR was used to detect the protein content and mRNA expression of spleen tyrosine kinase(Syk)/caspase recruitment domain protein 9(CARD9)/nuclear factor-κB(NF-κB)in spleen of each group.Results:Compared with control group,24 h-UTP,URBC,serum ALT,Scr,BUN,TNF-α,IL-1β,renal Syk,CARD9,NF-κB protein contents and mRNA expression levels of rats in model group were significantly increased(P＜0.01),while serum ALB was significantly decreased(P＜0.01).The pathological tissue damage of colon and kidney was obvious under light microscope,and strong clumpy IgA deposition was observed by immunofluorescence.Compared with model group,24 h-UTP,URBC,serum ALT,Scr,BUN,TNF-α,IL-1β,renal Syk,CARD9,NF-κB protein content and mRNA expression levels of rats in intervention groups were significantly decreased(P＜0.05,P＜0.01).Serum ALB was significantly increased(P＜0.01).The pathological tissue injury of colon and kidney was obviously improved under light microscope.Immunofluorescence showed decreased IgA deposition.Conclusion:Shenbining Granules can inhibit the immune inflammatory response of intestinal mucosa in IgAN rats and improve the pathological injury of colon and kidney by regulating the Syk/CARD9/NF-κB inflammatory signaling pathway.