CXC族趋化因子与糖尿病视网膜病变的实验研究

目的 研究ELR+及ELR- CXC族趋化因子在链脲佐菌素(STZ)诱导的糖尿病大鼠体内的表达.方法 34只健康雄性Wistar大鼠随机分为对照组(CON组,n=10)、糖尿病病程2个月组(DM2M组,n=12)和糖尿病病程4个月组(DM4M组,n=12).大鼠腹腔一次性注射STZ(65 mg/kg)建立糖尿病模型.伊文思蓝左心室灌注,视网膜铺片观察其微血管的增生情况；ELISA法检测各组大鼠血清、玻璃体、视网膜中各趋化因子表达并进行统计学分析；免疫荧光染色观察CXCR3在视网膜内表达情况.结果 DM2M组和DM4M组ELR+ CXC族趋化因子GRO、ENA-78、SDF-1及ELR- CXC趋化因子IP-10和MIG的表达量显著高于CON组(P＜0.01)；各趋化因子在DM4M组中表达量显著高于DM2M组(P＜0.05)；视网膜中表达量显著高于玻璃体与血清中表达量(P＜0.05).DM4M组及DM2M组视网膜中CXCR3高表达,且前者表达高于后者；其主要表达于视网膜颗粒细胞层及神经纤维层.结论 ELR+及ELR-CXC族趋化因子同时参与了糖尿病视网膜病变的病程进展,在调解血管增生及纤维化中可能发挥了重要作用.

Experimental research of relationship between CXC chemokines and diabetic retinopathy

Objective To investigate the expression of ELR+ and ELR-CXC chemokines in diabetic rats induced by streptozotocin(STZ).Methods Thirty-four healthy male Wistar rats were randomly divided into control group(CON group,n=10),diabetes mellitus 2 months group(DM2M group,n=12) and diabetes mellitus 4 months group(DM4M group,n=12).Rat diabetes model was induced by a single intraperitoneal injection of STZ(65 mg/kg).Left ventricular perfusion of Evens blue was performed,and microvascular proliferation was observed with retinal preparations.The expression of chemokines in the serum,retina and vitreous humor of each group was detected by ELISA,and statistical analysis was conducted.The expression of CXCR3 in retina was observed with immunofluorescence staining.Results The expression of ELR+ CXC chemokines of GRO,ENA-78,SDF-1 and that of ELR-CXC chemokines IP-10 and MIG in DM2M group and DM4M group was significantly higher than that in CON group(P<0.01).The expression of chemokines in DM4M group was significantly higher than that in DM2M group(P<0.05).The expression of chemokines in retina was significantly higher than that in vitreous humor and serum(P<0.05).The expression of CXCR3 in retina in DM4M group and DM2M group was relatively higher,especially for DM4M group,and the expression of CXCR3 was mainly found in the inner granular layer and nerve fiber layer.Conclusion ELR+ and ELR-CXC chemokines may participate in the development of diabetic retinopathy,which may play an important role in mediating vascular proliferation and fibration.