Inhibit the activity of CD4⁺CD28^null T cells to alleviate diabetic microvascular damage by blocking Kv1.3 channel

Objective To explore the feasibility of remitting diabetic microvascular damage by blocking CD4⁺CD28^null T cell viability used Kv1.3 channel blocker. Methods Total 80 cases diabetes mellitus in the Affiliated Hospital of Medical School of Ningbo University from January 2016 to December 2017 were selected, including diabetes mellitus (DM group), diabetic retinopathy (DR group), diabetic nephropathy (DN group) and diabetic retinopathy and nephropathy (DR+DN group), with 20 cases in each group. Meanwhile, 20 healthy volunteers were selected as the control group. Their CD4⁺CD28^null T cell proportion of peripheral blood was detected and extracted. Human vascular endothelial cells were cultured with 96-well plates, and divided into 5 groups: control group, CD28^null T intervention group, Kv1.3 block group 1, group 2, and group 3. In addition to the control group, CD4⁺CD28^null T cells were co-cultured with all groups. At the same time, Kv1.3 block group 1, group 2, and group 3 were interfered by 2 μL ADWX-1, with a concentration of 0.5 mg/mL, 1.0 mg/mL, and 2.0 mg/mL successively. The peak Kv1.3 potassium current, apoptosis rate of endothelial cells and concentration of INF-γ and TNF-α were measured 48 h later. Results The proportion of CD4⁺CD28^null T cells was increased successively in the order of the control group, DM group, DR group, DN group and DR+DN group, and the difference was statistically significant among the groups (all P<0.05). Compared with the control group, the endothelial cell apoptosis rate, INF-γ and TNF-α concentration of CD28^null T in the intervention group were significantly higher, compared with CD28^null T intervention group, those indexes in Kv1.3 block group 1, group 2 and group 3 was lower, and the difference was statistically significant among the different groups (all P<0.05). Conclusion Blocking Kv1.3 channel can inhibit the inflammatory damage to vascular endothelial cells induced by CD4⁺CD28^null T cells, which is of positive significance to alleviate diabetic microvascular disease.