Objective Present study aimed to research the mechanism of the use of 0.2% brimonidine tartrate eye drops in the treatment of optic nerve crush injury of rat.MethodsAnimal models of optic nerve crush injury were created in 60 SD female rats by clipping the exposed optic nerve at 2 mm in retrobulbar for 6 seconds with 78 grams of reverse forceps.The successful model was identified as Marcus-gun pupil without bleeding of fundus after operation.The animals were randomly assigned to model group and brimonidine treating group,and another 30 normal SD rats were used as the normal control group.The 0.2% brimonidine tartrate eye drops was topically administered at 2 hours before operation and after operation twice per day in the brimonidine treating group.The retinas from 18 rats were isolated after 3,7,21 days for RGCs counting by H&E staining,and the retinal ultrastructure was examined under the transmission electron microscope.The retinas from the other 72 SD rats (including normal,model and brimonidine groups) were prepared for the detection of bcl-2 and bax using immunohistochemistry l,3,5,7,14,21 days after the operation.ResultsNormal and almost normal retina structure was exhibited in rats of the normal group and brimonidine treating group,but disorder of cellular arragement and decrease of retinal thickness were found in the model rats under the optical microscope.The RGCs counting was significantly different among the three groups from 3 days through 21 days after operation with the considerably declination in the model group and brimonidine treating group compared with the normal control group (P＜0.05-0.01).However,that of the brimonidine treating group was obviously increased in comparison with the model group (P＜0.01).The expression of bax in rat retina was obviously reduced (P＜0.01),but the expression of bcl-2 was increased in brimonidine group compared with the model group from 5 through 7 days after operation (P＜0.01).ConclusionThe 0.2% brimonidine tartrate eye drops has a preventive effect on optic nerve crush injury of rat,and its inhibition on apoptosis is one of the mechanisms.

Objective To explore the effect and associated mechanism of fluvastatin combined with losartan on the expression of vascular endothelial growth factor (VEGF) in human podocytes induced by angiotensin (Ang)Ⅱ.Methods The differentiated human podocytes were cultured with various concentrations of Ang Ⅱ (10-9 to 10-5 mol/L) in vitro,followed by treatment of fluvastatin (10-7,10-6 and 10-5 mol/L),losartan (10-7,10-6 and 10-5 mol/L),extracellular signal-regulated kinase (ERK) inhibitor PD98059,and combination of fluvastatin and lolsartan.Expressions of VEGF and phosphorylation (p)ERK1/2 protein in podocytes were detected by Western blotting.RT-PCR was used to examine VEGF mRNA expression (P＜0.01).Results Ang Ⅱ up-regulated the expressions of VEGF and p-ERK1/2 in time-and dose-dependent manner.Above elevated expressions of VEGF and p-ERK1/2 induced by Ang Ⅱ could be down-regulated by fluvastatin,losartan and PD98059 respectively (P＜0.05).More obvious reduction of above expressions was found in combination of fluvastatin and losartan as compared to single agent (P ＜0.05).Conclusions Either fluvastatin or losartan can down-regulate the over-expression of VEGF and p-ERK1/2 induced by Ang Ⅱ in human podocytes,and their combination has a cooperative effect.The ERK signaling pathway may be one of the mechanisms of their renal protective effects.