Objective  To observe the effects of simvastatin on endothelial progenitor cells (EPCs) from peripheral blood and retinopathy in rats with diabetic retinopathy (DR). Methods  Eighty male Wistar rats were divided into normal control group (group A), DR model group (group B), DR with placebo group (group C), DR with simvastatin group (group D), with twenty rats in each group. The rats in group C and D received streptozotocin (STZ) injection to induce diabetic retinopathy. The rats in the group A and B were not intervened. The rats were gavaged with 20 mg/kg simvastatin (group D) or same volume of distilled water (group C) once a day. Flow cytometry was used to identify and count the number of EPCs from peripheral blood at the 1st，4th and 12th week after injection. Evans blue perfusion was used to detect the bloodretinal barrier (BRB) permeability. Immunohistochemical staining was used to observe the expression of CD31 in the retina. Real-time reverse transcriptionpolymerase chain reaction (RT-PCR) was used to measure the mRNA expression of eNOS, iNOS and Ang-1. The correlation between changes of EPCs and DR morphological changes was analyzed. Results  At the 1st，4th and 12th week after injection, compared with the group A, the number of EPCs was decreased in group C; Compared with the group B and C, the number of EPCs was increased in group D (t=4.967, 5.648, 6.688, 6.042, 7.392, 7.454;P＜0.05); there was no statistical difference of EPCs number between group B and C (t=0.525, -0.249, -0.619; P＞0.05), group A and D (t=6.733, 2.794, -5.535; P＜0.05) respectively. The structure of retina was continuous and its capillary structure was normal in control group. The retinal layers were edema and the retina developed telangiectatic vessels and many ganglion cells developed vacuolar degeneration in group B and C. The layers tissue of retina was less edema and gradually arranged in group D. The BRB permeability was significantly increased in group B and D compared with group A. The BRB permeability was significantly decreased in group D compared with group B (F=65.808，P＜0.05). The CD31 expression in group D was obviously higher than that in group A, B and C (F=24.799，P＜0.05). The eNOS expression in group B was obviously lower than that in group A, while in group D was obviously higher than that in group B (t=-2.750，2.230；P＜0.05). The iNOS and Ang-1 expression in group B were obviously higher than those in group A, while in group D was obviously lower than that in group B (t=3.881，-1.144，4.244，-1.458；P＜0.05). There was no difference in BRB permeability, eNOS, iNOS and Ang-1 expression between group B and C (t=0.480,-0.877, 0.062, 0.220; P＞0.05). Conclusions  Simvastatin could mobilize DR rats peripheral blood EPCs, induce migration and differentiation of retinal endothelial cell, slow down the DR progress by regulating the expression of endothelium factors such as eNOS and iNOS.

Citation： 张惟,韩琪,陈松,颜华. Effects of simvastatin on peripheral blood endothelial progenitor cells and retinopathy in rats with diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2012, 28(3): 258-263. doi: Copy