| Abstract:objective:To investigate the effects of peroxisome proliferator activated receptor-gamma (PPAR-γ) agonists on expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in retina in the earlier diabetic rats by use of PPAR-γagonists rosiglitazone interfereing the earlier diabetic rats, and elucidate the protective effect of PPAR-y agonists on diabetic retinopathy from the molecule level, and provide a new idea for prevention and early treatment diabetic retinopathy. Methods:One hundred and fourteen healthy male Wistar rats were chosen and divided into normal control group (C, 30), diabetes mellitus (DM,42), diabetes mellitus adding rosiglitazone (DM+rosiglitazone,42). Manufacture diabetes mellitus modle by intraperitoneal streptozocin (50mg/kg) injection. Immature rat model and death rats removed from the experimental groups. By experimental time point, the above three groups of rats were further divided into normal control 4w group (C 4w,10), normal control 8w group (C 8w,10), normal control 12w group (C 12w, 10), diabetes mellitus 4w group (DM 4w,10), diabetes mellitus 8w group (DM 8w,10), diabetes mellitus 12w group (DM 12w,10), diabetes mellitus adding rosiglitazone 4w group (DM+R 4w,10), diabetes mellitus adding rosiglitazone 8w group (DM+R 8w,10), diabetes mellitus adding rosiglitazone 12w group (DM+R 12w,10). In diabetes mellitus adding rosiglitazone groups(group 4w, 8w,12w), rosiglitazone (3mg/kg),a PPAR-γspecific agonist, was administered orally to rats once daily, from 3 days after the injection of the STZ. From the third day after injecting STZ, blood glucose and body weight were measured twice every week. After drug administration for 4w,8w and 12w rats were killed respectively,5 rats in each group were used to determine the blood-retina barrier permeability. Left eyeballs of the other 5 rats were removed. After retinal digest stretched preparation, the morphology of retinal microvascular changes were observed, the numbers of endothelial cells and perithelial cells were detected and E/P value was calculated. The right eyes of the same 5 rats were removed and paraffin embedded, detected MMP-2 and MMP-9 expression in the retina by immunohistochemistry, and the results were statistically analyzed. Results:(1) BRB permeability tests showed that the BRB permeability of DM 4w、8w、12w and DM+ R 4w、8w、12w groups were up-regulated manifestly in the corresponging time points in each group compared with group C(P<0.01). At all time points, DM+ R group compared with the corresponding DM group, the BRB permeability was significantly lower than the DM group, and a time-dependent change(P<0.01); but compared with the corresponging time point group C, BRB permeability were up-regulated(P<0.01). (2) Retinal digest stretched preparation showed that the blood capillary courser and the number and morphous of vessel wall cell were non apparent abnormality in DM 4w group as compared with control 4w and DM+ R 4w groups(P>0.05). But the number of the vessel wall P were significantly reduced, the number of endothelial cells were increased, capillary was tortuosity, diameter different diameters in DM 8w and DM 12w (P<0.01); At 8 weeks and 12 weeks, DM+ R group compared with the corresponding DM group, visible reduction in loss of vessel wall P, E proliferation were reduced, and that the change was time-dependent changes(P<0.01). (3) Immunohistochemistry showed that at each time point, the expression of MMP-2 and MMP-9 of DM 4w group, DM 8w group and DM 12w group were up-regulated in retina as compared with corresponding C group (P<0.01); At the corresponding experimental time points, the expression of MMP-2 and MMP-9 of the DM+R groups were up-regulated in retina as compared with corresponding C group (P<0.01), but the expression of MMP-2 and MMP-9 were down-regulated in retina as compared with DM groups (P<0.01). In C 4w、8w、12w groups, the expression of MMP-2 and MMP-9 were not significantly different in retina(P>0.05). The expression of MMP-2 and MMP-9 of DM 8w group were up-regulated as compared with DM 4w group in retina (P<0.01). The expression of MMP-2 and MMP-9 in retina of DM 12w group were up-regulated as compared with DM 4w group and DM 8wgroup (P<0.01). The expression of MMP-2 and MMP-9 of DM+ R 8w group and 12w group were up-regulated in retina as compared with DM+ R 4w group(P<0.01), but the expression of MMP-2 and MMP-9 of DM+ R 8w group were not statistically significant in retina as compared with DM+ R 12w group(P>0.05).Conclusion:(1) Diabetes mellitus modle by intraperitoneal streptozocin injection can be used for related research in early DR. (2) The MMP-2 and MMP-9 play an important role in the pathogenesis of early DR. (3) Rosiglitazone, a PPAR-γspecific agonist, can inhibit the MMP-2 and MMP-9 expression in the early DM rat retina, reduce the permeability of blood retinal barrier. |
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