[Influence of tert-butylhydroquinone on the islets function and expression of HO-1 and VEGF in retina of type 2 diabetic rats].

Objective To observe the effect of tert-butylhydroquinone (tBHQ) on the islets function and expression of HO-1 and VEGF in retina of type 2 diabetic rats. Methods Experimental study. Forty healthy male Sprague-Dawley rats with 6 weeks old were given high-fat and high-sugar diet for 4 weeks and then intraperitoneal injection with streptozotocin(STZ) 30mg/kg to induce diabetic model. Model group were further randomly divided into normal group and model group. Ten age matched health rats were chosen as control group. 4 and 12 weeks later, weight of rats , fasting blood glucose (FBG), fasting serum insulin (FINS), the levels of serum liqids were measured. The HO-1 and vascular endothelial growth factor (VEGF) expression in retina were determined by immunohistochmistry and quantitative real-time PCR. The differences of the mean values among the three groups were analyzed by one-factor analysis of variance. The multiple comparisons of the mean values among the three groups were analyzed by LSD-t analysis. Results Type 2 diabetic model was successfully established in 32 rats, the success rate was 80.0%. Compared with normal gourp, plasma triglyceride (TG), plasma total cholesterol (TC) and plasma low density lipoprotein (LDL-C) of diabetic rats increased dramatically, and plasma high density lipoprotein (HDL-C) decreased. FBG was significant different between all groups(χ24w=10.631, P4W=0.005; χ212w=15.053, P12w=0.001), and was significantly increased in tBHQ intervention group than that in diabetic group at the end of 12 week. The levels of FINS and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly higher , and insulin sensitivity index (ISI) was significantly lower in diabetic and tBHQ intervention group compared with normal group(P 0.05). The immunohistochemistry staining results showed the protein leveI of retinal HO-1 (F4w=689.535, P4w=0.000; F12w=287.988, P12w=0.000)and VEGF(F4w=1084.956, P4w=0.000; F12w= 1107.553, P12w=0.000) was significant different beteween all groups. The expression of HO-1 mRNA increased significantly in diabetic group(t4w=10.21, t12w=9.95)and tBHQ intervention group(t4w=14.01, t12w= 25.64)than that in normal group(P<0.05). The expression of HO-1 mRNA increased significantly in tBHQ intervention group(t4w=6.04, t12w=19.00)than that in diabetic group(P<0.05). The expression of VEGF mRNA increased significantly in diabetic group(t4w=11.92, t12w=29.27)and tBHQ intervention group(t4w=12.50, t12w= 11.24)than that in normal group(P<0.05). The expression of VEGF mRNA increased significantly in tBHQ intervention group(t4w=-6.36, t12w=-20.22)than that in diabetic group(P<0.05). Conclusion tBHQ can promote the secretion of insulin in diabetic rats, lowered glucose levels, also induce the expression of HO-1 and suppress the expression of VEGF in retina to confer protection to islets function and retina of type 2 diabtic rats. (Chin J Ophthalmol, 2016, 52:373-381) Key words: Diabetic retinopathy; Diabetes mellitus, experimental; Hydroquinones; Heme oxygenase-1; Vascular endothelial growth factor A