The Protective Effect Of Taurine On The Oxidative Damage In The Retina Of Diabetic Rats In The Early Stage

Background: Diabetic retinopathy (DR) is one of the major complications of Diabetic Mellitus (DM), and its etiological factor and pathogenetic mechanism is complex and involved in many factors. The effective prevention and permanent cure for DR are not available yet. Although some clinical treatments have been developed, including control of blood glucose, restraining the excessive expression of vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC), inhibiting of the protein non-enzymatic glycosylation and polyol pathway, their clinical effects are imperfect. Recently oxidative damage is recognized as a primary course led to complications of DM, resulting with an idea to treat DR by antioxidant intervention with many contradictions in term of it's effects. Therefore the effect of Taurine'intervention on preventing DR was studied and explored in this thesis.Purpose: To investigate the protective effect of taurine to the oxidative damage on the retina of diabetic rats in the early stage, discuss its action mechanism, and find out the reliable experimental data for the clinical application.Method: 75 live and healthy Wistar rats were chosen, and randomly divided into 4 groups in the study: normal control group (CON), diabetes control group (DM), taurine-treated group (D+Tau) and vitamin E-treated group (D+VE). Diabetic rats were established by intraperioneal injection of streptozotocin (STZ). Taurine and vitamin E were diluted into solution of 3% and 1% by using solution of 0.5% carboxymethylcellulose (CMC). D+Tau and D+VE groups received intragastric administration of 10 ml/kg·body weight by using the above solution of taurine and vitamin E once a day. CON and DM groups received the same amount of intragastric administration by using the 0.5% CMC at the same frequency and timing with the first two groups. The period of intragastric administration lasted 8 weeks. The level of fasting blood glucose was determined by using gluose oxidase method. Pathomorphology of rats'retina was analyzed by using hematoxylin and eosin (HE) staining and transmission electron microscopy. Expression of inducible nitric oxide synthetase (iNOS) was determined by immuneohistochemistry staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in retina were measured by chemistry chromatometry.Results: The diabetic models characterized by hyperglycemia were successfully obtained after 72 hours when Wistar rats were intraperioneal injected with STZ of 60mg/kg·body weight, and the incidence of diabetes is 83.33%. Before treatment, the level of blood glucose of DM, D+Tau and D+VE groups all increased largely (P<0.01) compared with CON group, while no significant difference observed among the groups. Comparison with pro- and post- treatments, no obvious difference of the blood glucose had been observed among CON, DM and D+VE groups; However the blood glucose of D+Tau group was lower than DM group (P<0.05), but still higher than CON group after the treatment(P<0.01); There was no appreciable difference of blood glucose found between D+VE and DM groups. For DM group, the array of membrane discs of photoreceptor cells distorted. Inner nuclear layer cells and ganglion cells swelled obviously while nucleus karyopyknosis shrank. The axon of nerve fiber swelled largely. Endothelial cells of capillaries swelled and lumen became narrow. For D+Tau group, microstructure damages of retina were slighter than DM group. For D+VE group, microstructure damages of retina were slighter than DM group,but still severer than D+Tau group. Compared with CON group, SOD activity decreased by 25.42% (P<0.01) while MDA content increased by 317.39% (P<0.01) in DM group. Compared with DM group, SOD activity increased by 25.1% (P<0.01) and MDA content decreased by 67.14% (P<0.01) in D+Tau group. The Activity of SOD increased by 24.59% (P<0.01) and the content of MDA decreased by 30.40% (P<0.01) in D+VE group. The numbers of iNOS positive cells in rats retina measured by mmunohistochemistry staining were 1.75±0.72 in CON, 25.20±0.84 in DM,13.07±0.93 in D+Tau,and 14.15±0.75 in D+VE group respectively. iNOS positive cells were rarely observed in retina tissue of CON group but increased a lot in DM group with a significant deference (P<0.01), most of them locating in ganglion cell layer and a few in inner nuclear layer. The number of iNOS positive cells decreased obviously (P<0.01) in D+Tau and D+VE groups compared with DM groups, only existing in ganglion cell layer. There is no significant difference on the number of iNOS positive cells between D+Tau and D+VE groups.Conclusions: Oxidative stress is involved in the early development of DR. Taurine reduces the level of blood glucose to some extent and has ability to eliminate free radicals and enhance the performance of retina antioxidation. Taurine can provide protection to the retina of the early diabetic rats to some extent, and the probably mechanisms include regulating the disturbance of glucose metabolism, diminishing MDA content and increasing SOD activity in retina, devaluating the expression of iNOS, and improving the microstructure damages in retina.