Preventive Effect Of Danhong Huayu Koufuye Combined With Metformin On Diabetic Retinopathy In Zucker Diabetic Fatty Rats

ObjectiveThe aim of the study was to evaluate the effect of Danhong Huayu Koufoye (DHK) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms.MethodsAt 13 weeks of age, ZDF rats were with average fasting blood glucose (FBG) higher than 13.0 mmol/L, and were then randomly divided into four groups (n=6):(1) ZDF+Vehicle group (distilled water,p.o.,3.2 mL/kg); (2) ZDF+Met group (metformin,p.o., 209 mg/kg); (3) ZDF+DHK group (DHK, p.o.,3.2 mL/kg); (4) ZDF+DHK+Met group (metformin and DHK, p.o.,209 mg/kg and 3.2 mL/kg, respectively). In addition, the age-matched lean rats were regarded as Lean+Vehicle group (distilled water, p.o.,3.2 mL/kg). All rats were treated for 19 weeks.FBG, body-weight, and 24 h diet intake, water intake and urine volume were assessed periodically. Effect of DHK or DHK+Met on DR was evaluated by retinal analysis of electrophysiology and histology.In addition, levels of insulin, glycosylated hemoglobin (HbA1c), hemorrheology indexes, lipidic indexes, platelet indexes, von Willebrand factor (vWF), malondialdehyde (MDA), intercellular adhesion molecule-1 (ICAM-1) and activity of superoxyde dismutase (SOD) were detected. Platelet aggregation rate was also assessed. HOMA-IR and HOMA-β were calculated as well.Results(1) DHK or Met alone had no effect on the prolongation of latency times and the decrease of amplitudes of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. However, DHK combined with metformin significantly reversed the prolongation of latency times of FERG and OPs.(2) DHK alone or in combination with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology, while Met had no retinal protective effect.(3) DHK alone or in combination with metformin remarkably reduced FBG and HbAlc levels, and improved HOMA-IR as well.(4) DHK alone or in combination with metformin remarkably reducted low density lipoprotein cholesterol (LDL-c) and triglycerides (TG) levels.(5) DHK significantly reduced levels of ICAM-1, vWF and MDA. DHK in combination with metformin significantly decreased MDA level.(6) DHK showed a remarkable reduction of PCT, MPV and platelet aggregation rate. DHK in combination with metformin remarkably decreased platelet aggregation rate.(7) DHK significantly reduced whole blood viscosity.ConclusionsDHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia and hyperlipidemia, reducing endothelial injury, improving platelet shape and function, and alleviating hemorrheology as well.