The Effect Of Eplerenone On Immune Response And CD4~+ CD25~+ Treg Cell Kv1.3 Potassium Channels In Patients With Chronic Heart Failure

Objective:To observe the cytokines of the peripheral blood of patients with chronic heart failure,the change of the proportion of Th17/Treg and the voltage dependence Kv1.3 potassium channel current of CD4⁺CD25⁺Treg cells（Treg）,to explore the immunological mechanism of the development of heart failure occurs,to provide a certain theoretical basis.Measure:Density gradient magnetic separation of CD4⁺CD25⁺Treg cells;examine the mean fluorescence intensity（MFI）of IL-2、IL-4、IL-6、IL-10、IL-17A、TNF、IFN-γin peripheral blood with Cytometric Bead Array（CBA）;Examine the proportion change of Th17/Treg with FACS;Examine the content of TGF-β、IL-10 with ELISA;Control cells were treated with Kv1.3 channel blocker Psora-4;The group CHF group Control does not interfere,Examine the electric current density changes of Kv1.3potassium channels in Treg cells;Examine the difference of Ca²⁺content in the group Control,CHF and group CHF⁺EPL CD4⁺CD25⁺Treg cells was detected by fluorescent probe.Result:Group CHF’s MFI of IL-2、IL-4、IL-6、IL-10、IL-17A、TNF、IFN-γare obviouly stronger than group Control（P<0.05）.There were significant differences in Th17/Treg ratio:group CHF vs.group Control[（2.97±0.86）vs（0.95±0.12）],（P<0.01）.The concentration of TGF-beta and il-10 in group CHF was significantly greater than that of group Control（P<0.01）.The current density of Kv1.3 potassium channels in the peripheral blood Treg cells in group Psora-4 was significantly lower than group Control:[（35.6±3.51）vs（106.11±10.47）]pA/pF,（P<0.01）.Group CHF Treg cells Kv1.3potassium channel current density peak was significantly higher group Control:[（259.57±19.07）vs（106.11±10.47）]pA/pF,（P<0.01）;Group CHF+EPL Treg cells Kv1.3potassium channel current density peak was significantly higher group CHF:[（41.21±3.61）vs（259.57±19.07）]pA/pF,（P<0.01）.There was no statistical difference between the group CHF and the group Control Treg cell membrane capacitance:CHF:Ctrl:CHF+EPL=（1.11±0.02）:（1.14±0.01）:（1.12±0.04）pF,（P>0.05）.The fluorescence intensity of CD4⁺CD25⁺Treg cells in peripheral blood of Control group was different from that in CHF group:[（15.60±4.84）,n=5]vs[（150.95±7.56）,n=6],（P<0.001）.Conclusion:The proportion of Th17/Treg cells increased,the cytokine of CHF were significantly increased;The Ca²⁺content in CHF group increased,and eplerenone can decreased it.EPL can change the current density of Kv1.3 potassium channel in CD4⁺CD25⁺Treg cells,suggesting that it may participate in the function regulation of Treg cells.