The Changes Of Rat Models With Intraocular Hypertension On The Quantity Of Endothelial Progenitor Cells From Peripheral Blood And Intervention Of Simvastatin

Objective:1. To establish animal model of elevated intraocular pressure (IOP) in Wistar rats, and to study the expression of apoptotic cells in retina of elevated IOP with the extension of disease.2. To study the changes of endothelial progenitor cells (EPCs) in peripheral blood in rats with elevated IOP on the quantity of from with the extension of disease.3. To discuss the effect of Simvastatin to the apoptotic cells in retina and the changes on the quantity of EPCs from peripheral blood in rats.4. To discuss the improvement of Simvastatin to retina of in rats with elevated IOP, and to provide a theoretical basis for the optical nerve protection.Methods:1.One hundred and fifty male Wistar rats weighted220-250g with three months old were involved in this study. They were randomly divided into normal control group elevated IOP group and laser group. Elevated IOP group model were manipulated with corneoscleral limbus vein cauterization. All rats in elevated IOP group were divided into five sub-group according to the duration, which were designated as group three days, seven days,three weeks, two months, and three months. Mice in laser group model were manipulated with comeoscleral limbus vein lateral cauterization, by avoidance blood vessel. The quantity of EPCs from peripheral blood were compared, among five sub-groups and laser group observations of HE staining retina were made with light microscopy. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). Cells localized with Bcl-2/Bax were analysised by immunohistochemistry method.2.Thirty rats were selected randomly from ninety rats in elevated IOP group and were taken Simvastatin orally with20mg/kg daily continuously twenty for days as the intervention group. Twenty rats were took saline orally as blank control group. Another fifty rats were as positive control group. The rats in intervention groups were divided into six sub-groups, according to the duration, which were designated as group three days, seven days and three weeks respectively. Among the three sub-groups, the quantity of EPCs from peripheral blood were compared. Observations of HE staining retina of mice on three weeks after intervention were made with light microscopy. At the same time, cell apoptosis was detected by TUNEL and cells localized with Bcl-2/Bax was analysised by immunohistochemistry method. Results:1. The IOP elevated to the peak three days after laser treatment and, gradually slowed down, but still higher than normal IOP8mmHg above, that could maitain a higher level for more than three months. In laser group, the IOP also reached a peak at day three and then gradually decreased. The number of EPCs in peripheral blood reached the peak at day three, and then slowly reduced in ocular hypertension group and in the laser group, while the IOP in elevated IOP group decreased more significant (p<0.05).2. The HE staining retina was no significant, compared with normal group, in elevated IOP on groups three days, seven days and three weeks. While in elevated IOP two months sub-group, the pathological changes of thinner layers of the retina to outer nuclear layer for the most, and the loss of ganglion cells could be observed. In elevated IOP three months group, the pathological changes were more significant.3. Compared with normal group, elevated IOP three days and seven days sub-groups, Bcl-2/Bax staining showed no significant. While in mice with elevated IOP three weeks, two months and three months, the cells localized with Bcl-2/Bax were significantly increased. The apoptosis cells were increased gradually along with the duration of elevated IOP.4. Observations of HE staining retina showed no significantce elevated IOP between mice in elevated IOP three weeks group and in intervention group. Cells with Bcl-2/Bax were significantly decreased and the apoptosis cells were significantly decreased as well.Conclusion:1. By using laser, we successfully established animal model of elevated IOP in rats. The number of EPCs in peripheral blood of high intraocular pressure reached to the peak and then slowly decreased.2. The apoptosis cells of photoreceptors were increased gradually along with the duration of elevated IOP.3. Simvastatin might play a role during the restore of the retina damage in mice with elevated IOP rats.