Protective Effect Of Rapamycin On Ischemia-reperfusion Induced Injury In Retina Of Rat

Objective To study the protective effects and the mechanism ofrapamycin (RAPA)on ischemia-reperfusion-induced injury in retina of rat，and whether the protective effect by reducing hypoxia-inducible factor-1α(HIF-1α) to achieve.Methods75healthy Wistar rats were used in the study. All of therats were divided into three groups randomly: in normal (blank) controlgroup,and in experimental group, each group was25rats.RIR was inducedin control group and in experimental group Wistar rats by increasingintraocular pressure via an intracameral catheter. the experimental group ratsunderwent a intraperitoneal injection with rapamycin(2mg/kg)2hoursbefore retinal ischemia; and in the control group, saline water and dimethylsulfoxide were injected correspondingly. The observation morphology ofRGCs and the thickness of the inner retinal layers was measured by HE staining method before and0,6,12,24,and48hours after reperfusion.TdT-mediated biotin-dUTP nick end labelling (TUNEL) staining techniquewas used to examine the apoptosis of RGCs. The levels of HIF-1αmRNAwere analyzed by Realtime PCR assay. The levels of HIF-1αprotein wereanalyzed by western-blotting assay.Results (1) In the early period of retinal ischemia-reperfusioninjury,the edematous status of experimental group （137.55±7.76）μm waslighter than that of the control group（162.26±6.41）μm,and less RGCsvacuolar phenomenon. At6hours after reperfusion, the thickness of theinner retinal layers of experimental group was greater than that of thecontrol group (P<0．05).(2) At12hours after reperfusion, the apoptotic cellsin experimental group was obvious lower than that in the control group (P<0.05).(3) RAPA declined the expression of HIF-1αmRNA in experimentalgroup,the difference between experimental group and control group wasstatistically significant (P<0．05)．(4)The expression of HIF-1α proteinpresent parabola tendency after ischemia-reperfusion injury and peak on12h.the difference between experimental group and experimental control groupwas statistically significant(P<0．05)．Conclusion RAPA can protect the retina from ischemia-reperfusioninjury．The downregulation of hif-1αmaybe involved in the mechanism ofthe protection．...