糖尿病视网膜病变患者血清Gas6和SDF-1的检测及意义

摘要

背景 糖尿病视网膜病变(DR)是常见的糖尿病微血管并发症之一,发病机制复杂.研究表明生长停滞特异性基因产物6(Gas6)/TAM系统参与了糖尿病及其并发症的发生,而2型糖尿病患者基质细胞衍生因子1(SDF-1)表达水平发生改变,但血清Gas6/TAM系统和SDF-1是否参与DR的发生尚不明确.目的 比较正常人和糖尿病患者血清Gas6和SDF-1水平的变化,探讨其在DR发病过程中的作用.方法 采用前瞻性队列研究方法,于2013年1-8月收集在南方医科大学第三附属医院诊治的糖尿病患者90例,按1987年中华医学会糖尿病视网膜病变分期标准将患者分为增生型DR(PDR)组、单纯型DR(BDR)组、糖尿病无视网膜病变(NDR)组,每组30例,另纳入同期在医院进行健康体检的正常志愿者30名.收集正常志愿者和糖尿病患者外周血2 ml,检测受试者白细胞和中性粒细胞计数及血清甘油三酯(TG)、总胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平.采用ELISA法检测受试者血清中Gas6、SDF-1α和SDF-1β水平,比较正常志愿者与DR患者上述检测指标的差异,并分析患者血清中Gas6、SDF-1α和SDF-1β质量浓度与血细胞及血脂水平的关系. 结果 正常对照组、NDR组、BDR组和PDR组血清中CHOL分另为4.93 (4.14,5.44)、5.02(4.35,5.69)、4.54(3.85,5.93)和5.99(5.11,6.89) mmol/L,其中PDR组血清中CHOL浓度明显高于正常对照组、NDR组和BDR组,差异均有统计学意义(P=0.002、0.007、0.006).正常对照组、BDR组白细胞计数高于PDR组(P=0.034、0.015),BDR组中性粒细胞计数高于PDR组(P=0.024),NDR组HDL-C高于PDR组(P=0.032).PDR组LDL-C水平高于正常对照组(P=0.032).与正常对照组相比,NDR组和BDR组患者血清Gas6水平明显下降,差异均有统计学意义(P=0.048,P=0.006),而PDR组患者血清Gas6水平高于BDR组,但差异无统计学意义(P=0.297).PDR组患者血清中SDF-1α水平明显高于BDR组(P=0.033);PDR组、BDR组患者血清中SDF-1β水平明显高于NDR组(P=0.011、0.008)和正常对照组(P=0.030、0.002).患者血清中Gas6质量浓度与血清中CHOL、TG、LDL-C浓度间均呈微弱正相关(r=0.285、0.200、0.241,P＜0.05),血清中SDF-1α水平与SDF-1β水平间呈微弱正相关(r=0.190,P=0.038);血清中SDF-1β质量浓度与白细胞计数呈微弱正相关(r=0.183,P=0.045).以血清Gas6为因变量,以白细胞、中性粒细胞、CHOL、TG、HDL-C、LDL-C、SDF-1α、SDF-1β为自变量进行多元逐步回归分析,得到回归方程:Gas6=170.791 +5.283CHOL(F=5.021,P=0.027). 结论 2型糖尿病导致的DR患者血清中Gas6、SDF-1α、SDF-1β水平在DR的发生和发展过程中可能发挥一定的作用,其作用机制可能与血糖水平、炎性细胞和脂质代谢紊乱或新生血管形成有关.%Background Diabetic retinopathy (DR) is a progressive vision-threatening complication of diabetes mellitus (DM),but its pathogenic mechanism is still unclear.Researches showed that growth arrest-specific gene product 6 (Gas6) /TAM system participates in pathogenesis and development of DR,and stromal-derived factors (SDF) vary in 2-type DM patients.However,whether Gas6/TAM and SDF-1 are associated with DR is below understood.Objective This study was to determine the relationship between the staging of DR and the levels of serum Gas6,SDF-1α and SDF-1β in DM patients.Methods A prospective cohord study was designed in this study.Ninety 2-type DM patients were included in the 3rd Affiliated Hospital of Southern Medical University Hospital from January to August in 2013.The patients were grouped into the non-diabetic retinopathy (NDR) group,background DR group (BDR) and proliferative DR (PDR) group,with 30 for each group.Thirty normal volunteers were enrolled in the same hospital and same period.The periphery blood 2 ml was collected from all the subjects under the consent inform.The levels of serum Gas6,SDF-1α and SDF-1β were assayed by ELISA,and leukocytes,neutrophils,plasma triglycerides (TG),total cholesterol (CHOL),high density lipoprotein cholesterol (H DL-C) and low density lipoprotein cholesterol (LDL-C) levels were detected and compared among the 4 groups.The correlations of serum Gas6,SDF-1 α and SDF-1 β changes with blood inflammatory cells and blood lipid were analyzed.Results The plasma CHOL concentrations were 4.93(4.14,5.44),5.02(4.35,5.69),4.54(3.85,5.93) and 5.99(5.11,6.89)mmol/L in the normal control group,NDR group,BDR group and PDR group,respectively,and the blood CHOL concentrations were significantly higher in the PDR group than those of the normal control group,NDR group,BDR group (P =0.002,P =0.007,P =0.006).White blood cell counts in the normal control group,BDR group were higher than those of the PDR group (P =0.034,P =0.015),neutrophil counts in the BDR group were higher than those of the PDR group (P =0.024),HDL-C in the NDR group was higher than that in the PDR group (P =0.032).LDL-C in the PDR group was higher than that in the normal control group.Compared with the normal control group,serum Gas6 levels were significantly lower in the NDR group and BDR group (P =0.048,P =0.006),and the serum Gas6 level showed an insignificant increase in the PDR group in comparison with BDR group (P =0.297).Serum SDF-1α levels in the PDR group was significantly higher than that in the BDR group (P =0.033) ;serum SDF-1β levels in the PDR group,BDR group were significantly higher than that in the NDR group (P =0.011,P =0.008) and normal control group (P =0.030,P =0.002).Weaker positive correlation was observed between the serum Gas6 and CHOL,TG,LDL-C levels (r=0.285,r=0.200,r=0.241,all at P＜0.05),between SDF-1α and SDF-1β (r=0.190,P＜0.05) as well as between SDF-1β and white blood cell (r=0.183,P＜0.05).Serum Gas6 served as dependent variable,while white blood cell,neutrophil,CHOL,TG,HDL-C,LDL-C,SDF-1α,SDF-1β served as independent variables,multiple stepwise regression analysis showed Gas6 =170.791 + 5.283CHOL (F =5.021,P =0.027).Conclusions Serum Gas6,SDF-1α and SDF-1β probably participate in the development of DR in 2-type diabetic patients.Gas6,SDF-1 α,SDF-1 β may play roles by affecting blood glucose level,angiogenesis,inflammatory cells and blood lipid metabolism.