Mechanism Of IL-17-Mediated NF-κB Signaling Pathway In Kidney Injury Induced By Diquat Poisoning In Rats

Objective:To explore the mechanism of IL-17-mediated NF-κB signaling pathway in kidney injury induced by diquat(DQ)poisoning in rats.Methods:120 male SD rats were randomly divided into 4 groups: normal control group(N),IL-17 inhibitor control group(N+IL-17i),DQ exposure group(DQ),and IL-17 inhibitor treatment group(DQ+IL-17i),and then divided into 12 h,24h and 72 h subgroups according to observation time points(10 rats in each subgroup).Group n and group N+IL-17 i were intraperitoneally injected with 30mg/kg normal saline,while group DQ and group DQ+IL-17 i were intraperitoneally injected with 0.2% diquat solution 30mg/kg to model.after 30 minutes of successfu L modeling,group n and group DQ were intraperitoneally injected with 30mg/kg normal saline at the same time twice/24 h.DQ+IL-17 i group and N+IL-17 i group were intraperitoneally injected with the same dose of IL-17inhibitor(Y-320)at the same time,and the drug was continuously used for up to 3 days until they were killed.Blood was collected from femoral vein after anesthesia at the above three time points,and markers of kidney injury such as Cr,BUN,C-ysc,NGAL and KIM-1 were detected,and the content of IL-17 was detected Partial detection of ROS expression,KIM-1 and NAGL gene expression,NF-κBp65 and IκBαprotein content were detected.Results:1.the rats in DQ group and DQ+IL-17 i group showed behavioral manifestations after poisoning,but there was no poisoning in N group and N+IL-17 i group.The values of BUN,Cr,C-ysc,NGAL and KIM-1 in DQ group increased significantly at 12 h,24h and72h(p < 0.05).after using Y-320,the values of BUN,Cr,C-ysc,NGAL and KIM-1 in DQ+IL-17 i group were all at 12 h,24h and 72 h.The mrna levels of NGAL and Kim-1 in DQ group began to increase at 12 h,and were most obvious at 72h(p < 0.05).after Y-320 was used,the mrna levels of NGAL and Kim-1 in DQ+IL-17 i group were significantly lower than those in DQ group at 12 h,24h and 72h(p < 0.05).4.After exposure to DQ group,the pathological damage and pathological score of kidney gradually increased at12 h,24h and 72 h,with the most obvious at 72 h.After using Y-320,the pathological damage and pathological score of kidney in DQ+IL-17 i group were significantly reduced compared with DQ group at 12 h,24h and 72 h,and there was no poisoning in N group and N+IL-17 i group.5.The level of IL-17 in DQ group began to increase at 12 h,and was the most obvious at 72h(P < 0.05).After using Y-320,the level of IL-17 in DQ+IL-17 i group decreased significantly at 12 h,24h and 72 h compared with DQ group(P < 0.05).6.After exposure to DQ,the expression of ROS in kidney tissue increased at 12 h,24h and 72 h,with the most obvious at 24h(P < 0.05).After using Y-320,the expression of ROS in kidney tissue of DQ+IL-17 i group decreased at 12 h,24h and 72 h,and the most obvious was at 24h(P < 0.05).7.After exposure to DQ,the contents of SOD and MDA began to increase at 12 h,which was the most obvious at 72h(P < 0.05).After using Y-320,the contents of SOD and MDA in DQ+IL-17 i began to decrease at 12 h,which was the most obvious at 72h(P < 0.05).8.In DQ group,the content of IκBα protein decreased at 12 h,24h and 72 h after exposure(P < 0.05),while the content of NF-κBp65 protein did not increase significantly at 12h(P > 0.05),but increased significantly at 24 h and 72h(P <0.05).After using Y-320,the content of IκBα in DQ+IL-17 i group decreased at 12 h.Conclusion:Inhibition of IL-17 can decrease the expression of NF-κB,and can reduce the kidney damage caused by DQ poisoning,which indicates that the mechanism of kidney injury induced by DQ poisoning may be related to the activation of NF-κB signaling pathway by IL-17.