The Role And Mechanism Of Periodontal Microbial Diversity In Regulating TLRs Signaling Pathway In IgA Nephropathy

Objective: Periodontitis stimulates the host cells to release inflammatory factors through the control of TLRs signal pathway,and then causes the immune inflammatory reaction,to promote the progression of IgAN.Methods: High-throughput sequencing technology was used to analyze the oral microbial diversity of Uygur patients and screen the dominant flora.The expression levels of TNF-α,IL-6,IL-1β and other related inflammatory factors in oral peripheral blood,periodontal tissue and kidney tissue of rats were detected,and the levels of TLR4,TLR9,NF-κB in tissues were detected.Rat renal mesangial cells were isolated and cultured in vitro to block the TLR4/9 signaling pathway of mesangial cells.The expression levels of inflammatory factors and m RNA levels of TLR4,TLR9 receptor and NUCLEAR transcription factor NF-κB were detected before and after blocking.The correlation between IgAN and chronic periodontitis and its mechanism were determined.Results: Our study showed that saliva levels of Neisseria and Tannerella in the periodontitis+IgA nephropathy group were significantly higher than those in the periodontitis group at the genus level.Compared with IgA nephropathy group,Porphyromonas and Haemophilus were significantly higher in genus level.The m RNA and protein levels of TLR4 and TLR9 in periodontal and renal tissues of rats in periodontitis +IgA group were higher than those in IgA,IgA and IgA group,and NF-κB p-p65 was significantly higher than that in IgA group(0.827±0.031,0.699±0.038).The periodontitis+IgA group had more periodontal and renal pathological changes than the other groups.TLR4 inhibitor significantly inhibited l PS-induced TLR4 and NF-κB m RNA expression in cultured mesangial cells(2.475±0.289,0.610±0.132;3.277±0.331,2.208±0.619),TLR4,TLR9,NF-κB P-P65protein(0.770±0.039,0.597±0.019;0.744±0.015,0.533±0.024;0.698±0.029,0.541±0.039).TLR4 and TLR9 inhibitors can down Periodontal microorganisms LPS-induced IL-1β,IL-6 and TNF-α in supernatant of cultured mesangial cells.Conclusion: Periodontal pathogens can activate NF-κB through TLR4/9,release inflammatory factors and aggravate periodontitis and IgA nephropathy,providing a new clinical and basic research direction for the diagnosis and treatment of IgA nephropathy.