[Protective effect of valproic acid on ischemia-reperfusion induced injury in retina of rat].

OBJECTIVE: To study the protective effects and the related mechanism of valproic acid (VPA) on ischemia-reperfusion-induced injury in retina of rat.

METHODS: Experimental study. Ninety Wistar rats were divided randomly into three groups: normal (blank) control group, retinal ischemia-reperfusion (experimental control) group treated with PBS, retinal ischemia-reperfusion (experimental) group treated with VPA. Retinal ischemia was induced by acute high intraocular pressure. Rats were executed at 6, 12, 24, 48 h and 7 d after reperfusion. The eyeballs were enucleated for retinal histopathological examination. The fluoro-gold retrograde labeling was performed and the survival of retinal ganglion cells was analyzed by calculating the densities in fluoro-gold labeled retinal ganglion cell. The protein expression of heat shock protein 70 (Hsp70) and the acetylation of transcription factor Sp1 were analyzed by Western blot assay. The levels of bcl-2 and bax mRNA were analyzed by RT-PCR assay. To determine the significance of differences, analysis of paired-samples t-test was carried out.

RESULTS: (1) The HE staining of retinal histological section showed that the edema of retina were attenuated significantly by VPA in experimental group, the difference between the experimental group and the experimental control group was statistically significant (t = 7.491, P < 0.05). The fluoro-gold retrograde labeling showed that the survival of retinal ganglion cells in experimental group [(1629 ± 63)/mm(2)] was significantly higher than experimental group [(908 ± 65)/mm(2)], the difference between the two groups was statistically significant (t = 7.248, P < 0.05). (2) The immuno-blot analysis showed that VPA resulted in significant increase in expression of Hsp70 protein in ischemic retinas, the difference between experimental group and experimental control group was statistically significant (t = 6.176, P < 0.05). The acetylation of Sp1 was significantly higher in experimental group than experimental control group, the difference between the two groups was statistically significant (t = 11.264, P < 0.05). The RT-PCR analysis showed that VPA increased the expression of bcl-2 mRNA in experimental group (0.403 ± 0.009), the difference between experimental group and experimental control group (0.314 ± 0.012) was statistically significant (t = 5.489, P < 0.05). VPA attenuated the expression of bax mRNA in experimental group (0.383 ± 0.009), the difference between experimental group and experimental control group (0.492 ± 0.016) was statistically significant (t = 5.723, P < 0.05).

CONCLUSIONS: (1) VPA protected retina from ischemic injury. (2) The upregulation of Hsp70 and bcl-2, downregulation of bax maybe involved in the mechanism of the protection.