Protective Effect Of Curcumin On STZ - Induced Diabetic Retinopathy

Objective：To investigate the potential protective effects of Curcumin on retina indiabetic mice induced by STZ. And then explore the possible mechanisms, in order toprovide some valuable evidences for clinical application of Cur.Methods：SD mice were intraperitoneally injected of streptozotocin (STZ) for4weeks to generate type2diabetes mouse model as indicated by fasting plasmaglucose levels≥11.6mmol/L. The mice were divided into4groups: normal controlmice (N), normal mice treated with200mg/Kg/day Cur (Cur), diabetic mice (DM),diabetic mice treated with200mg/Kg/day Cur (DM+Cur). Give the Cur and DM+Cur group rats with curcumin200mg/kg/d by intragastric administration，Curcuminwith0.5%sodium carboxymethyl cellulose (CMC-Na) configured to mix suspension,irrigation to twelve weeks.At the same time the normal control group and diabeticgroup were accepted the same amount of carboxymethyl cellulose. Regularmonitoring of blood glucose and body weight changes during the experiment.Cur wasintroduced to mice by intragastric administration daily. After12weeks ofadministration, the mice were euthanized and eyes were dissected. Retinal histologywas examined.Expression levels of Bax and Bcl-2in retina tissues were determinedby western blotting.Results:1. before the experiment, N groups, Cur group, DM group and DM+Curgroup rats weight were (201.1±3.1)g,(202.2±3.5)g,(198.3±7.0)g,(197.2±5.4)grespectly.There was no statistically significant difference between the groups:compared Cur group and N group, there was no statistically significant difference (P=0.673,P>0.05); Compared the DM group and N group, there was no statisticallysignificant difference (P=0.167,P>0.05); Compared DM+Cur compared group and Ngroup, there was no statistically significant difference (P=0.172,P>0.05). to twelveweeks, N groups, Cur group, DM group and DM+Cur group rats weight were(470.3±4.1)g,(465.2±5.2)g,(275.2±4.3)g,(400.2±3.8)g respectly:during the experiment,N group rats weight increased steadily, till twelve weeks to gain weight (470.3±4.1)g;Cur group rats weight increased steadily, till twelve weeks to gain weight (465.2±465.2)g, there was no statistically significant difference compared with Ngroup (P=0.224, P>0.05); DM group rats weight increase slowly, till twelve weeks togain weight (275.2±4.3)g, weight drops than N group, there was obvious statisticalsignificance difference compared with N group (P<0.05); DM+Cur group of rats gainweight (400.2±3.8)g till twelve weeks, DM+Cur group of rats weight fell than the Ngroup (P<0.05), higher than the DM group (P<0.05).2. before the experiment, N groups, Cur group, DM group and DM+Cur group ratsblood glucose were (4.2±0.3) mmol/L，(4.1±0.2) mmol/L，(4.5±0.3) mmol/L，(4.4±0.2)mmol/L respectly. There was no statistically significant difference between the groups:compared Cur group and N group, there was no statistically significant difference (P=0.866, P>0.05); Compared the DM group and N group, there was no statisticallysignificant difference (P=0.074, P>0.05); compared DM+Cur group and N group,there was no statistically significant difference (P=0.110, P>0.05). to twelve weeks,N group, Cur group, DM group and DM+Cur group rats blood glucose were(4.6±0.6)mmol/L,(4.5±0.2)mmol/L,(28.4±0.5)mmol/L，(16.7±0.7)mmol/L respectly:During the experiment, the N group rats and Cur group rats blood glucose was in therange of normal level (2.5-5.1mmol/L),to twelve weeks, the blood glucose of Ngroup rats was (4.6±0.6) mmol/L, the blood glucose of Cur group rats was (4.5±0.2)mmol/L, compared with the N group, there was no statistically significant difference(P=0.502, P>0.05); DM group and DM+Cur group blood sugar after the building isalways higher than the N group, DM group rats blood glucose with longer time andcontinue to rise, to twelve weeks, the blood glucose of DM group rats was (28.4±0.5)mmol/L, compared with the N group, the difference was statistically significant(P<0.05);compared with DM group,DM+Cur group blood glucose rise slowly, totwelve weeks, the blood glucose of DM+Cur group rats was (16.7±0.7)mmol/L,compared with DM group,DM+Cur group blood sugar rise slowly, and less than DMgroup, the difference was statistically significant (P<0.05).3. histological observation showed that the basic structure of rat retina divided into10layers, each layer is arranged orderly, the size of the cell is normal, inner membrane continuously complete, intact.Ganglion cells were monolayer,larger nucleus，round oroval in shape，with light staining，neatly arranged；The inner layer consists of4-5layer of cells，nuclei stained slightly larger,slightly darker；the outer nuclear layerthick,composed of10layers of cells，the nucleus is small，the dyeing depth,arrangedmore closely. The rat retina of DM group membrane, swelling in the outer nuclearlayer, fracture, thickening, rough, occasional capillary endothelial cells in the innermembrane. Hierarchical fuzzy, Some cells appear nuclear pyknosis phenomenon,cavitation and, disordered arrangement of cells, reducing the number and arrangementof sparse, especially outside the nuclear layer. the retina changes of DM+Cur grouprats were slighter than DM group.4. Western blot results showed that: compared with the normal group, DM group inretinal tissue increased Bax expression(P=0.0017,P<0.01),the difference wasstatistically significant;decreased the Bcl-2expression (P=0.0076,P<0.01), thedifference was statistically significant;Reduced the ratio of the Bcl-2/Bax, thedifference was statistically significant (P<0.01). Compared with DM group, DM+Curin retinal tissue decreased the Bax expression(P=0.0145, P<0.01), the difference wasstatistically significant;enhanced the Bcl-2expression(P=0.0081,P<0.01), thedifference was statistically significant；Increased the ratio of Bcl-2/Bax, the differencewas statistically significant(P<0.01).Conclusions：Cur can reduce the blood glucose, ameliorate the body weight loss ofdiabetic mice. Meanwhile, Cur can attenuate diabetes-induced apoptosis in retinalneurons by inhibiting the expression of Bax protein and increasing the ratio ofBcl-2-to-Bax, which suggested that Cur might be used to prevent retinal neuronaldamage in diabetes mellitus. In sum, Cur can be used to prevent and treat diabeticretinopathy.