DPP-4抑制剂对T2DM患者T淋巴细胞DPP-4/CD26表达及血LPS/TLR4水平的影响

目的：研究DPP-4抑制剂（DPP-4 inhibitor）常规治疗是否影响2型糖尿病患者T淋巴细胞CD26、脂多糖/Toll样受体-4（Lipopolysaccharide/toll like receptor-4，LPS/TLR-4）介导的炎症反应；T淋巴细胞CD26与血LPS/TLR-4介导的炎症反应之间是否存在可能的相关性。方法：自2017年11月至2018年3月，从武汉市第一医院门诊收集受试者。选择目前使用二甲双胍但血糖控制不佳的2型糖尿病患者（7% < HbA1c < 10%）130名，随机分为2组，一组为实验组（二甲双胍片0.5 g tid+磷酸西格列汀片100 mg qd）；另一组为对照组（二甲双胍片0.5 g tid+格列齐特缓释片30 mg qd）。用药3个月，检测用药前后2组患者一般生化水平、血糖、血脂、T淋巴细胞CD26、T淋巴细胞/单核细胞TLR-4阳性百分比、LPS的水平。结果：用药后两组T细胞表面CD26阳性百分比（%）分别为（12.26±12.3）vs（22.74±18.9），对照组高于实验组（P<0.05）；T淋巴细胞TLR-4平均表达水平分别为（17.34±10.9）vs（23.42±17.9），对照组高于实验组（P<0.01）；单核细胞TLR-4阳性百分比（%）分别为（18.67±10.6）vs（23.72±19.3），对照组高于实验组（P<0.01）。在所有2型糖尿病患者中：T细胞CD26与单核细胞TLR-4正相关，r=0.869（P<0.01）；T细胞CD26与LPS正相关，r=0.698（P<0.01）；单核细胞TLR-4与LPS正相关，r=0.816（P<0.01）。结论：DPP-4抑制剂抑制T细胞CD26、单核细胞表面TLR-4的表达水平；LPS、单核细胞TLR-4与T细胞CD26的表达正相关，提示常规治疗剂量的DPP-4抑制剂可能影响2型糖尿病患者的非特异性炎症反应，其临床意义值得进一步观察和验证。

DPP-4 inhibitors influence DPP-4/CD26 expressed on T cell and the LPS/TLR4 in patients of type 2 diabetes

OBJECTIVE To investigate whether conventional treatment of DPP-4 inhibitors impact the inflammatory response mediated by CD26 expressed on T lymphocyte and LPS/TLR-4(Lipopolysaccharide/toll like receptor-4) and the probable relationship of LPS/TLR-4 and the expression of CD26 on T cell. METHODS From October 2017 to March 2018, subjects were recruited from outpatient of the first Hospital of Wuhan. 130 patients with type 2 diabetes mellitus who currently use metformin but have poor blood glucose control (7% < HbA1c < 10%) were selected.All the patients were randomly divided into two groups:the experimental group (Metformin 50 mg tid and ceglitine 100 mg qd) and the control group (Metformin 50 mg tid and gliclazide sustained-release tablet 30 mg qd).Treatment regimen continued for 3 months. The biochemical level, blood glucose, blood lipid,CD26 expressed on T lymphocytesl、TLR-4 expressed on monocyte/T lymphocytes was examined before and after the study. RESULTS As to CD26 expressed on Tcell, the positive percentage of the two groups were (12.26±12.3) vs (22.74±18.9)(P<0.01),the control group is higher than the experimental group.As to TLR-4 expressed on T lymphocytesl, the positive percentage of the two groups were (17.34±10.9) vs (23.42±17.9),the control group is higher than the experimental group(P<0.01). As to TLR-4 expressed on monocyte, the positive percentage of the two groups were (18.67±10.6) vs (23.72±19.3),the control group is higher than the experimental group(P<0.01). CD26 expressed on T cell was positively correlated with TLR-4 expressed on monocyte, r was 0.869 (P<0.01); CD26 expressed on T cell was positively correlated with LPS, r was 0.698 (P<0.01). TLR-4 expressed on monocyte was positively correlated with LPS、TLR-4 expressed on T lymphocyte, r was respectively 0.816,0.763(P<0.01).LPS was positively related with CD26、TLR-4 expressed on monocytes,r was respectively 0.689,0.763 (P<0.01). CONCLUSION DPP 4 inhibitors may suppress CD26 expression on T cells and TLR-4 expressed on monocyte in T2DM; LPS,TLR-4 expressed on monocyte are positively correlated with CD26 expression on T lymphocytesl, indicating that standard doses of DPP 4 inhibitors may influence the nonspecific immune response in type 2 diabetes mellitus (T2DM); the clinical significance of which are worthy of further discussion.