| Objective:Objects:1) To establish hyperuricemia rat model induced by yeast extract combined with oxonic acid potassium salt (OA), the level of Serum uric acid as an examination indexes;2) Through rosuvastatin intervene in hyperuricemia rats, appraisal Morphology, function and molecular biology indicator;3) Comprehensive analysis, evaluation Clinical efficacy and dosage and action mechanism of rosuvastatin on hyperuricemia rats. Methods:1) yeast extract combined with Different doses of oxonic acid potassium salt (OA),64SD rats randomly grouped, except the control group, all groups treated with yeast extract powder (YEP) as21g·kg-1·-d-1; OA paired20g/L mother liquor with sterile distilled water, intragastric feeding as50mg-1·kg1-·d-1、100mg-1·kg-1·-d-1、200mg-1·kg-1·d-1or intraperitoneal injection as50mg-1·kg-1·d-1、100mg-1·kg-1·d-1、200mg-1·kg-1·d-1respectively for28days。The serum level of uric acid (UA), urea nitrogen (BUN) and creatinine (Cr) was detected with the commercially available detection kits, and the changes in histomorphology of kidney, heart and artery was assessed by histopathology, metabonomics analysis; establish hyperuricemia rat model;2)72SD rats randomly grouped as control group, modeling group, modeling+Ros2.5mg·kg-1·d-1(RL), modeling+Ros5.0m g·kg-1·d-1(RM), modeling+RoslOmg·kg-1·d-1(RH), modeling+ALL53.57m g·kg-1·-d-1. yeast extract powder (YEP) given as21g·kg-1·-d-1OA paired20g/L mother liquor with sterile distilled water, intraperitoneal injection as200mg-1·-kg-1·d-1, Rosuwastatin paired5mg/lml mother liquor with sterile distilled water, given for six weeks. The serum level of uric acid (UA), urea nitrogen (BUN) and creatinine (Cr) was detected with the commercially available detection kits, and the changes in histomorphology of kidney, heart and artery was assessed by histopathology and Metabonomics analysis suggest that the fat metabolism, sugar metabolism and amino acid metabolism, meet the hyperuricemia metabolic disorder. Results:Compared to the control without treatment, there was significant increase in serum level of UA in the groups of intragastric feeding with YEP alone, YEP combined with50-200mg OA/kg or intraperitoneal injection with YEP combined with50～100mg OA/kg, but no remarkable effect on animal kidney, heart or artery was found. When the dosage of intraperitoneal injection with YEP combined with OA was maximized to200mg OA/kg, we not only detetcted a high serum UA level but aldo observed morphological and pathological changes in rat kidney, heart and arteries. We established a rat model of hyperuricemia which showed an increase of UA, ET-1and AngⅡ content in serum as well as a decrease of NO in serum and eNOS expression in tissue specimens of aorta, as an important profile for altered endothelial function of the experimental animal model and representing a clear contrast to the normal control. After treatment of the animal model with rosuvastatin, we found that the drug has improved the profile of endothelial function and gradually recovered to the normal level, and the curative effect was remarkably higher than the allopurinol group (positive control) at the dosage of10mg rosuvastatin/kg and intervention time of6weeks compared to the normal control group, whereas there were significant differences with the animal model without treatment. Conclusions:The treatment of the rats with YEP combined with200mg OA/kg by intraperitoneal injection may an optimal dosage for the preparation of persistent and stable hyperuricemia animal model, and may also become a favorable model for study of pathological damages related to secondary cardiovascular diseases caused by hyperuricemia. Our results suggested that rosuvastatin had a remarkable curative effect on endothelial dysfunction of rats caused by hyperuricemia, and to restore the profile related to endothelial function altered by hyperuricemia may be an important mechanism of the pharmacological response of the drug. |
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