| Objective:To explore the mechanism of IL-23/IL-17 axis and the immunological regulation of azithromycin through the IL-23 / IL-17 axis way by observing the change of blood and urine biochemical markers and the serum levels of IL-23,IL-17 in rats with Adriamycin-induced nephrosis.Methods:All of the 135 male Wistar rats were fed 1 week to adapt the enviroment.All the rats were randomly divided into 5 groups: blank control gruop,model gruop,azithromycin intervention group, prednisone intervention group and united intervention group.The model of Adriamycin-induced nephrosis was induced by a tail intravenous injection of adriamycin for 2 times.The injection doses were 4mg/kg and3.5mg/kg.24 h urinary protein(24n UP) were measured in 4th week.The models of Adriamycin-induced nephrosis were successful with 24 h UP>100mg/kg,and the differences between the model gruop and the 3 intervention groups were not statistically significant. The rats of the 3 intervention groups were treated drugs accordingly per day.The doses of prednisone and azithromycin were 12.5mg/(kg?d)and 62.5mg/(kg ?d).The rats of blank control group and model group were treated water at the same time.The 24 h UP,Ucr,Tp,Alb,Glo,Tcho,Scr were measured and the Ccr was calculated in the 4th,6th,8thweek.Enzyme-linked immunosorbent assay was used to quantify the serum IL-23,IL-17 with the rats of the 5 groups at the 4th,6th,8th week.Results:1.The comparison of the 24 h urinary proteinAt the end of 4th week,the 24 h UP of model gruop,azithromycin intervention group,prednisone intervention group and united intervention group>100mg/d,which proved the model was successful.2.The comparison of the blood and urine biochemical markers between 5 groups(1)The comparison of the blood and urine biochemical markers at the same time between 5 groups(1) Compared with blank control group,24 h UP,Scr,Tcho were higher,and Tp,Alb,Ccr were lower in model group,azithromycin intervention group,prednisoneintervention group and united intervention group in the 4th week(P<0.05).(2) Compared with model group,24 h UP,Scr,Tcho were lower,and Tp,Alb,Ccr were higher in azithromycin intervention group,prednisone intervention group and united intervention group in the 6thweek(P<0.05).The change in united intervention group of the blood and urine biochemical markers was the most obvious.(3)In the 8th week,24 h UP,Scr,Tcho in azithromycin intervention group,prednisone intervention group and united intervention group were lower than those in model group,and Tp,Alb,Ccr were higher(P<0.05). The most obvious change of the blood and urine biochemical markers was in united intervention group.(2)The comparison of blood and urine biochemical markers between the different times in the same group(1)There were no significant difference of blood and urine biochemical markers in blank control group between 4th,6th,8thweek(P>0.05).(2)Compared with the 4th week in model group,24 h UP,Scr,Tcho were higher in the 6thweek(P<0.05),and Tp,Alb,Ccr were lower(P<0.05).Compared with the 6th week in model group,24 h UP,Scr,Tcho were higher in the 8th week(P<0.05),and Tp,Alb,Ccr were lower(P<0.05).(3)Compared with the 4thweek in 3 intervention groups,24 h UP,Scr,Tcho were lower in the 6th week(P<0.05),and Tp,Alb,Ccr were higher(P<0.05).Compared with the 6thweek in 3 intervention group,24 h UP,Scr,Tcho were lower in the 8th week(P<0.05),and Tp,Alb,Ccr were higher(P<0.05).3.The level of IL-23,IL-17 in serum(1) The serum levels of IL-23,IL-17 in model group,azithromycin intervention group,prednisone intervention group and united intervention group were higher than those in blank control group in the 4th week(P<0.05).There were no significant difference between the model group and 3 intervention group(P>0.05). The serum levels of IL-23,IL-17 in intervention groups were lower than those in model group in the 6th,8th week(P<0.05).The decline of the serum levels was the most obvious in united intervention group(P<0.05).(2)The IL-23,IL-17 levels of model group were higher in 6th,8th week than thosein 4th week(P<0.05),and those in 8th week were higher than those in 6th week(P<0.05).The IL-23,IL-17 levels of intervention groups were lower in 6th,8th week than those in 4th week(P<0.05),and those in 8th week were lower than those in6thweek(P<0.05).4.The biochemical markers of liver function:There were no significant differences between model group, azithromycin intervention group,prednisone intervention group and united intervention group on the levels of the biochemical markers that represented the liver function.5.The correlation analysis:The levels of IL-23,IL-17 in model group were positively correlated with 24 h UP(r=0.784,r=0.865,P<0.05).The level of IL-23 was positively corrlated with the level of IL-17(r=0.730,P<0.05).The levels of IL-23,IL-17 in azithromycin intervention group were positively correlated with 24 h UP(r=0.756,r=0.804, P<0.05).The level of IL-23 was positively corrlated with the level of IL-17(r=0.682,P<0.05).The levels of IL-23,IL-17 in prednisone intervention group were positively correlated with 24 h UP(r=0.803,r=0.858, P<0.01).The level of IL-23 was positively corrlated with the level of IL-17(r=0.793,P<0.05).The level of IL-23,IL-17 in united intervention group were positively correlated with 24 h UP(r=0.800,r=0.888,P<0.05).The level of IL-23 was positively corrlated with the level of IL-17(r=0.873,P<0.01).Conclusion:1.IL-23/IL-17 axis may play a role in the mechanisms of proteinuria and pathology of the rats with Adriamycin-induced nephrosis.2.Azithromycin may inhibit the IL-23/IL-17 axis' activity to relief the Adriamycin-induced nephrosis.3.Azithromycin may have the same inhibition towards IL-23/IL-17 axis with prednisone,and azithromycin may enhance the effectiveness of prednisone. |
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