Influence of hypoxia-inducible factor-1α on the expression of neutrophil CD18 and leukocyte adhesion in diabetic rats / 中华眼底病杂志

ABSTRACT

Objective To observe the influence of the expression of CD18 on the neutrophile and the leukocyte adhesion to retinal vascular endothelium by hypoxia-inducible factor-1 alpha (HIF-1α) in early diabetic retinopathy rats. Methods Male Sprague-Dawley rats received intraperitoneal injection of streptozotocin to induce diabetes model. 18 diabetic rats were divided into 3 groups randomly after 2 months of diabetes induction, including diabetic group (group B), HIF-1α anti-sense oligonucleotides (ASODN) injection group (group C) and HIF-1α sense oligonueleotides (SODN) injection group (group D), the age and weigh matched health rats were chosen as control group (group A), with 6 rats in each group. Then group A and B rats received 5 % glucose solution caudalis veins injection, group C and group D rats received HIF-1α ASODN and HIF-1α SODN caudalis veins injection, respectively(0.25 mg/kg). The level of CD18 on the neutrophil isolated from the peripheral blood was measured by flow cytometry. Retinal leukostasis was quantified with acridine orange leukocyte fluorography. Results The percentage of CD 18 positive neutrophil cell was (44.93±3. 60)% in group B, (18.66±1.52)% in group A, (31.66±4.72)% in group C,(51.00±5.66)% in group D. Compared with each other groups,the differences are statistically significant (F= 42. 46, P<0.001). The number of positive staining cells of retinal leukocyte was (46.16±10.68)in group A, (133.83±20.43)in group B, (99.83±9.28)in group C, (121.33±10. 23) in group C. Compared group B with group C,the number of positive staining cells raised about 2.89 times;compared group B with group C and D,the differences are statistically significant (P= 0.12, 95% confidence interval -3.69～28. 69 ). Conclusions In vivo, HIF-1α can decreased the expression of CD18 on neutrophils from diabetic rats' peripheral blood and the collection of retinal leukos- tasis in the diabetic animals. HIF-1α may serve as a therapeutic target for the treatment and/or prevention of early diabetic retinopathy.