Abstract:

Objective To investigate the expression and location of ELR+CXC chemokine receptors （CXCR1, CXCR2 and CXCR4）and ELR-CXC chemokine receptor (CXCR3) in the retina of diabetic rats. Methods Forty male SD rats were randomly divided into normal control group (M0 group, n=10), diabetes mellitus 2 months group (M2 group, n=10), diabetes mellitus 4 months group (M4 group, n=10) and diabetes mellitus 6 months group (M6 group, n=10). The animal model of diabetes mellitus was induced by intraperitoneal injection of 1% streptozotocin (STZ, 60 mg/kg). The retinal morphology was observed with Evans blue perfusion and HE staining, the expression of CXC chemokine receptors in the retina was detected by Western blotting, and the location of CXC chemokine receptors in epiretinal membranes was determined by immunohistochemical staining. Results The expression of ELR+CXC chemokine receptors CXCR1 in M2 group was significantly higher than that in M0 group (P<0.01). The expression of CXCR2 in M4 group and M6 group was significantly higher than that in M0 group (P<0.05), and the expression of CXCR2 in M6 group was significantly lower than that in M4 group (P<0.05). The expression of CXCR4 in M4 group and M6 group was significantly higher than that in M0 group (P<0.01), and the expression of CXCR4 in M6 group was significantly higher than that in M4 group (P<0.05). The expression of ELR-CXC chemokine receptors CXCR3 in diabetes mellitus groups was significantly higher than that in M0 group (P<0.05), and was increased with the age (P<0.05). Immunohistochemical staining revealed that there was no obviously expression of CXCR1 in the retina of each group. CXCR2 was detected occasionally in the inner limiting membrane and inner granular layer in M4 group and M6 group. CXCR3 was detected in the retina of all diabetes mellitus groups, and CXCR3 mainly located around blood vessels and in the inner granular layer. CXCR4 was detected in all diabetes mellitus groups, which mainly located in the inner limiting membrane, and gradually expanded to the inner granular layer. Conclusion The expression and location of CXC chemokines receptors are different in rats with different ages. The expression and location of promoting vascularization factors (CXCR1, CXCR2 nd CXCR4) and inhibiting vascularization factor CXCR3 change with severity of diabetes mellitus, which to some extent can reflect the progress of diabetic retinopathy, and may offer new targets for blocking the progress of diabetic retinopathy at the early period.

Key words: CXC chemokine receptors, diabetic retinopathy, animal model of diabetes mellitus