| Objective:This study aimed to investigate the expression of IL-23 in the kidney of Adriamycin(ADR)nephropathy mice and the mechanism of IL-23 acting on??T cells by IL-23R and resulting in the change of Th17/Treg,and the effects of prednisone on the immunologic balance axis of IL-23/IL-23R-??T-Th17/Treg in the kidney of this model.Methods:Healthy male BALb/c mice were randomly divided into control group,ADR group,ADR with low dose of prednisone[ADR+Pre(low)]group,and ADR with high dose of prednisone[ADR+Pre(high)]group.At the beginning of the 5th week after setting up ADR model,ADR+Pre(low)group and ADR+Pre(high)group were treated with prednisone by gavage once a day for 8 weeks at a dose of13.5mg/kg body weight and 18.0mg/kg body weight respectively.The concentration of random urinary protein was measured by the Coomassie brilliant blue method.The concentration of random urinary creatinine was measured by creatinine assay kit.The pathological changes of kidney were observed by pathological HE staining and transmission electron microscope(TEM).The expression of IL-23 in the kidney was measured by immunofluorescence.The percentage of total??T,IL-23R~+??T,IL-17~+??T,Th17 and Treg cells in the kidney were measured by flow cytometry.Results:As time progresses,compared with control group,we found that the pathological manifestations of the kidney specimens in ADR group were gradually changed from minimal change nephrotic syndrome(MCNS)to focal segmental glomerulosclerosis(FSGS),the random urinary protein-creatinine ratio(RUPCR)was significantly increased(p<0.001).The IL-23 expressed in glomeruli was significantly increased(p<0.0001).In the kidney of ADR group,the percentage of total??T,IL-23R~+??T,IL-17~+??T and Th17 cells were significantly increased(p<0.05),Treg cells showed no significant differences,and the Th17/Treg ratio was gradually imbalanced(p<0.01).Compared with ADR group,the kidney injury in 2 treatment groups had different levels of remission,the RUPCRs were all significantly decreased(p<0.001),moreover,the RUPCR in ADR+Pre(high)group was lower than that in ADR+Pre(low)group(p<0.05).The glomerular IL-23 in 2 treatment groups were significantly lower than that in ADR group(p<0.0001),and the glomerular IL-23 in ADR+Pre(high)group was significantly lower than that in ADR+Pre(low)group(p<0.001),but the 2 treatment groups were still higher than control group(p<0.01).The percentage of IL-23R~+??T and IL-17~+??T cells in 2 treatment groups,compares with ADR group,were significantly decreased(p<0.05),but the percentage of the total??T cells in 2 treatment groups were significantly increased(p<0.01).In the kidney of ADR+Pre(high)group,compared with ADR group,the percentage of Th17 was gradually decreased(p<0.05),Treg showed no significant differences,and the Th17/Treg ratio was gradually decreased(p<0.05).Conclusion:As the expression of glomerular IL-23 of ADR mice increased,the IL-23R-expressing??T cells up-regulated,and the IL-17-producing??T cells increased,then the Th17/Treg ratio imbalance aggravated,finally the kidney injury got worsen.The treatment with sufficient prednisone in early time can down-regulate the expression of IL-23inglomerulianddelayTh17/Tregimbalancethrough IL-23/IL-23R-??T-Th17/Treg axis,thus protecting the kidney.The increase of total??T cells in the kidney after the treatment with prednisone may suggest that there are some other subcategories of??T cells involved in the process of protecting kidney. |
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