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

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

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。

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%<HbA1 c<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 T2 DM;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(T2 DM);the clinical significance of which are worthy of further discussion.