Protective Action Of Liraglutide On Damage Of Retinal Photoreceptor Cells In Type Ⅰ Diabetic Mice

Objective:Our study intends to elucidate the protective effect of Liraglutide(LR) to the retinal on type 1 diabetes(T1D) mice model, and to explore its mechanism, provide the basis for its clinical application.Method:T1D mice, intraperitoneal injection of STZ 85mg/kg injection 2 times,interval of five days. Thirty normal mice were randomly divided into negative control group, positive control group (5000 lux,72 h) and treated group. The treated group is classified with LR Ⅰ (62.5 μg/kg weight), LR Ⅱ (175 μg/kg weight) and LRⅢ(250μg/kg weight), repectively injected every day, continuously for 10 dayss of light (50001ux) for 72 hours. Each group of 6 mice,The control groups were injected with physiological saline. The mice were killed, paraffin sections were measured for eyeballs, observe the morphology by HE staining, count retinal outer nuclear layers, and use the method of immunohistochemistryity to test the expression of p-Erk 1/2 protein. Statistical analysis by one-way ANOVA and t-test.Result:1.Observation of the morphology and retinal outer nuclear layers counting:In contrast with T1D control group, all treated groups of LR(11.93±0.86,13.38±1.46, 13.61±1.66) increased significantly (P<0.001), while there’s no statistical difference when compared with negative control group.2.immunohistochemistry test results show that, compared with the control group, the treatment group p-Erkl/2 liraglutide mice retina photosensitive cellexpression was significantly increased (P<0.05), and in a dose effect relationship.3. Expression of 3 thioredoxin Trx gene:expression of Trx was down regulated indiabetic mice. LR Ⅰ (0.75 ± 0.13, P<0.05), LR Ⅱ (1.11 ± 0.09, P<0.001), LR Ⅲ (0.83 ± 0.11, P<0.01) and diabetic light group compared to Trx all up-regulated.4. The expression of ASK:Compared with light group,the expression amount of ASK in LR I (0.20±0.003,P < 0.001), and LR Ⅱ (0.24±0.009,P < 0.01) and LR III(0.20±0.003,P < 0.001) were both down-regulated.Conclusion:Liraglutide could up-regulate the expression of antioxidant related protein which mediated by p-Erk 1/2 and Trx, down-regulate the expression of Apoptosis associated proteins which mediated by ASK and protect the oxidative damage of retinal photoreceptor cells caused by Type 1 diabetes and light injury.