Effects of Kv1.3 inhibitor margatoxin on polarization of M1 macrophages and renal inflammation and injury in mice with renal injury
Objective:To observe the effect of voltage-gated potassium channel isoform(Kv)1.3 inhibitor,margatoxin(MgTx),on macrophage(MØ)polarization and renal inflammation and injury in mice with unilateral ureteral obstruction(UUO).Methods:Forty-eight male C57BL/6J mice were randomly and equally divided into four groups:Sham group,Sham+MgTx group,UUO group,UUO+MgTx group,with 12 mice in each group.The Sham group underwent simple open and closed abdominal surgery,with daily intraperitoneal injection of noraml saline after operation;Sham+MgTx group underwent open and closed abdominal surgery,with daily intraperitoneal injection of MgTx after surgery;UUO group underwent UUO operation,with daily intraperitoneal injection of normal saline after operation;UUO+MgTx group underwent UUO operation,with daily intraperitoneal injection of MgTx after operation.On the 3rd and 7th day after operation,six mice in each group were anesthetized,and whole blood was collected from the eyeballs,then the mice were immediately euthanized and kidney tissue was harvested.Renal injury was assessed by HE staining;protein levels of Kv1.3,TGF-β1 and α-SMA were detected by Western blotting;changes of peripheral blood monocytes and renal MØ polarization were analyzed by flow cytometry;mRNA levels of M1 and M2 biomarkers were detected by qRT-PCR.Results:Compared with Sham group,UUO group showed obvious renal injury and inflammation,and the relative expression levels of Kv1.3,TGF-β1,α-SMA were significantly increased(P<0.001).Compared with UUO group,renal injury was reduced,and relative expression levels of Kv1.3,TGF-β1 and α-SMA were greatly decreased in UUO+MgTx group(P<0.001).In addition,compared with Sham group,the proportion of M1 type MØ in peripheral blood monocytes and kidney tissues,and the relative expression level of M1 type MØ marker related mRNA weresignificantly increased(P<0.01),while the relative expression level of M2 type MØ marker related mRNA were obviously decreased in UUO group(P<0.01).Compared with UUO group,the proportion of peripheral blood mononuclear cells and M1 type MØ in renal tissues were significantly decreased in UUO+MgTx group,the relative mRNA expression levels of M1 type MØ marker were significantly decreased(P<0.01),while the mRNA levels of M2 type MØ markers were greatly increased(P<0.01).Conclusion:Kv1.3 inhibitor MgTx could inhibit MØ polarization towards M1 and attenuate renal inflammation and injury in UUO mice.
万方数据
维普
