Effect of valsartan and fluvastatin on the expression of glycogen synthase kinase-3β in retina of diabetic rat / 中华实验眼科杂志

ABSTRACT

Background Glycogen synthase kinase-3β (GSK-3β)plays an important role in glucose metabolism,and it may be affect the occurrence of diabetic retinopathy(DR).ObjectiveThe present study was to investigate the effect of valsartan and fluvastatin on the expression of GSK-3β in retina of diabetes rat model.MethodsDiabetes mellitus models were induced by intrapenetoneal injection of streptozotocin(STZ) in 47 clean Sprague-Dawley(SD) rats and were then randomedly divided into 4 groups.Ten other normal rats were served as normal control group.Sodium carboxy methyl cellulose solution,valsartan,fluvastatin,valsartan+fluvastatin and sodium carboxy methyl cellulose solution was given by oral once per day for 12 weeks respectively in diabetes control group ( n =12),valsartan group ( n =12 ),fluvastatin group ( n =11 ),valsartau + fluvastatin group ( n =12 ) and normal control group.Twelve weeks after administration of drugs,blood glucose was measured and compared among various groups,and the expression of p-GSK-3β ( Ser-9 ) protein in retina was quantified and located by Western blot and immunohistochemistry,respectively.Results Twelve weeks after use of drugs,the level of blood glucose was(5.28±0.30),(26.08±3.33 ),(26.03 ±2.66 ),(25.90± 2.86 ),(25.99 ± 2.14 ) mmol/L in the normal control group,diabetes control group,valsartan,fluvastatin,valsartan + fluvastatin group,respectively,showing a significant difference among the 5 groups ( F =110.74,P＜0.01 ).Western blot showed that the grey value of p-GSK-3β ( Ser-9 ) /β-actin in retina in the diabetic control group was significant higher than the normal group(2.774±0.139 vs 1.927±0.111,q =15.79,P＜0.01 ),and that in valsartan,fluvastatin,valsartan+fluvastatin group was lower than the diabetic control group ( 1.895 ±0.090,2.051 ± 0.113,1.537 ± 0.071 vs 2.774 ± 0.139 ) ( q =1 3.69,13.48,23.06,P ＜ 0.01 ).The grey value of p-GSK-3β (Ser-9)/β-actin in the valsartan+fluvastatin group was declined in comparison with the valsartan group and fluvastatin group ( q =6.67,9.58,P＜0.01 ).Immunohistochemistry showed that the p-GSK-3β(Ser-9) protein was expressed all over the retinal layers and obviously in retinal ganglion cell layer(GCL) in normal control group.But the p-GSK-3β(Ser-9) protein was expressed significantly in diabetic control group.The expression of p-GSK-3β (Ser-9)protein was attenuated both in valsartan and fluvastatin groups and further attenuated in valsartan + fluvastatin group. Conclusions p-GSK-3β (Ser-9) protein is overexpressed in GCL of retina of diabetes rat.Both valsartan and fluvastatin can inhibit the expression of p-GSK-3β (Ser-9) and even getting stronger when they combined.