The Effects Of Rapamycin On Retinal Ischemia-reperfusion Injury Of Rats And The Expression Of Caspase-7 And Calpain-1

Objective To observe the effect of rapamycin(RAPA)on the expression of caspase-7 and calpain-1 in retinal ischemia-reperfusion injury(RIRI)of rats.Methods Sixty-five healthy SD rats were randomly divided into three groups: normal group(5 rats),ischemia-reperfusion group(30 rats)and therapy group(30 rats).The last two groups were respectively divided into 0h,2h,6h,12 h,24h and 48 h subgroups.RIRI models were induced in ischemia-reperfusion group and therapy group by increasing intraocular pressure via a booster device.Normal group received no treatment.The rats in therapy group underwent the intraperitoneal injection with RAPA(2mg/kg)2hours before retinal ischemia,and the ischemia-reperfusion group with the same dose of normal sodium and DMSO.Rats in each group were sacrificed at different time points and eyes were removed immediately.Specimens were made into paraffin sections.Retinal tissue of different time points were stained by HE staining.The morphological changes of retina were observed and the thickness of inner retinal layer were measured.Immunohistochemistry was used to detecte the expression of caspase-7 and calpain-1.Results During the early period of RIRI,the edema of retina was increased in ischemia-reperfusion group than that of normal group.In ischemia-reperfusion group,cells arranged a bit of loose,number of retinal ganglion cells(RGC)decreased and in vacuolar degeneration compared with the normal group in the late stage.The inner retinal layer thickness was less in therapy group than that of ischemia-reperfusion group at 0h and 2h after RIRI.At 6h later after reperfusion,the inner retinal layer in therapy group were thicker compared with the ischemia-reperfusion group(all P<0.05),while the vacuolar phenomenon was also less.The expression of caspase-7 reached the peak at 24 h after reperfusion.In therapy group,the expression of caspase-7were obviously lower than those in ischemia-reperfusion group at 6h,12 h,24h and 48 h after RIRI(all P<0.05).At 6h after reperfusion,the expression of calpain-1 reached the peak.Except 48 h after reperfusion,the expression of calpain-1 were decreased compared with ischemia-reperfusion group at the other time points.Conclusion RAPA can protect the retina from RIRI,and the down-regulation of caspase-7 and calpain-1 may be involved in the mechanism of the protection.