The Research On Function And Intervention Of Toll-like Receptor9 In Glomerulonephritis

PurposeTo investigate the function of TLR-9 on the onset and development of glomerulonephritis, providing theoretical basis on opening up special antagonistic drug for glomerulonephritis.MethodsThe MsPGN model is applied in our study. 55 wistar rats were randomly divided into five groups:①Normal group(N group);②Anti-Thy1.1 nephritis Model group(M group);③CpG-ODN injection Group I(CPG group);④GpC-ODN group(GPC group);⑤CpG-ODN injection Group II (DCG group) ;⑥Leflunomide group(LTG group);⑦Prednisone group(PTG group);⑧Leflunomide+Prednisone group(LPG).Twenty-four-hour urine were drawn to determine twenty-four-hour Urine protein for each rats at regular stage.,Before rats were sacrificed, collect the blood sample from heart for determination of Renal function and serum albumin. At the same time ,renal tissue was obtained.Then we performed the pathological examination,NF-κB immune-histochemistry and RT-PCRwhich was to determine the mRNA expression of TLR9,INF-γand IL-6.See to the main body abour the detail collecting methods and management.Results1. Biochemical indicator: there is no significant difference in blood urea nitrogen and creatinine between groups in the research. Compared with Group M, the seralbumin in DTG group decreases obviously and has significantdifferences with P<0.05. While compared with DCG group,ALB in Group LTG,PTG and LPG is higher, there is statistical significance with P< 0.05.2. Urine protein: Compared with Group M, there is significant differences between Group M and other groups(P<0.05). Compared with Group DCG, Group LTG ,PTG and LPG were severely reduced from the second week with significantly statistical differences(P<0.05), among which the LPG group decreased the worst with P<0.01.3.Changes of TLR9,IL-6 and IFN-γ: mRNA expression of TLR9 and IL-6 in DCG group increased evidently,and has significant differencs with M group. Compared with M group,mRNA of TLR9 in LTG group decreased, has significant differencs, but IL-6 and INF-γmRNA hasn't; mRNA of TLR9,IL-6 and IFN-γin PTG and LPG group all reduced,and exists significant differencs with P<0.01. Compared with LPG group,three indexes in PTG group all decreased which has singnificant differencs with P<0.01.ConclusionThe expression of chemotatic factor and its receptor introduced by TLR9 can aggratate the biochemistry and pathological changes of glomerulonephritis.Leflunomide and Prednisone can downregulate the expression of TLR9 respectively, the combination of which has a synergistic effect. This provides theoretical basis on opening up special antagonistic drug for glomerulonephritis.