Carbon Dots Compound 180 Combined With Potassium Oxonate Induced Gout Model In Mice And Its Application

Gout is an inflammatory disease caused by abnormal purine metabolism,increased uric acid production,or poor uric acid excretion.Gout is difficult to cure,and the pain tends to recur.In severe cases,it can lead to complications such as hypertension,chronic kidney disease,and cardiovascular and cerebrovascular diseases,seriously affecting the daily life and physical health of gout patients.Currently,the main drugs used for the treatment of gout include colchicine,februstat,and others.Due to the side effects of these drugs such as diarrhea,abdominal pain,drug allergy,and susceptibility to drug resistance,there is currently no recognized and comprehensive drug for the treatment of gout.Therefore,it is of great significance to develop new and safe gout treatment drugs.In the process of new drug development,the activity screening of compounds and the preclinical evaluation of drug readiness are important tasks.At this time,a stable gout model is very important for new drug development.However,currently,the gout model reported in the literature has shortcomings such as instability and poor repeatability,which greatly limits its application in the activity screening of drugs for treating gout.In this study,we prepared a carbon dots compound 180 using carbon nanodots,which have attracted widespread attention in recent years.We used carbon dot compounds in combination with uric acid oxidase inhibitors to induce hyperuricemia and gouty nephropathy models,and evaluated the models.Firstly,we prepared the carbon dots compound 180 by hydrothermal method.In vitro experiments,deposition of uric acid experiments showed that carbon dots compound 180 can effectively deposit uric acid to form urate precipitation over time.A gout model can be established using the function of carbon dots compound 180 to deposit urates.In vivo experiments,hyperuricemia and gout models were induced using potassium oxyzinate,a uric acid oxidase inhibitor,in combination with carbon dots compound 180.Secondly,this study established a stable gout model by inducing gout in mice using potassium oxyzinate combined with carbon dots compounds 180,and evaluated the animal model.The experiment was divided into a model group and a control group.The model group was treated with 300 mg/kg of potassium oxyzinate and1800.7 mg/kg of carbon dots compounds by gavage,while the control group was treated with an equal amount of physiological saline by gavage.After 30 days of treatment,the model group and the control group were tested for blood indicators,Gomori method for uric acid salt staining,and small animal CT in vivo.The results showed that the gout model induced by potassium oxazinate combined with carbon dots compound 180 could last from 30 days to 80 days or even longer.The uric acid test results of intragastric or injection treatment showed that one and a half hours after intragastric administration,the serum uric acid in mice significantly increased,consistent with the symptoms of hyperuricemia,indicating that potassium oxyzinate combined with carbon dots compound 180 can induce hyperuricemia;The Gomori staining results showed that in the model group of potassium oxazinate combined with carbon dots compound 180,uric acid salt precipitates appeared in the kidney of mice,and the uric acid salt precipitates appeared earlier when potassium oxazinate combined with carbon dots compound 180 was administered by gavage than when administered by injection,indicating that potassium oxazinate combined with carbon dots compound 180 can induce gouty nephropathy model;In vivo CT results of small animals showed that gout stones appeared in the joints of mice in the model group treated with potassium oxazinate combined with carbon dots compound 180,which means that potassium oxazinate combined with carbon dots compound 180 can induce gouty arthritis models in mice.Finally,we prepared two carbon dots compounds,AC-CDs and PD-CDs,by microwave digestion.In the experimental design,colchicine,benzbromarone,and allopurinol were used as positive controls,and normal saline was used as negative controls.The gout model induced by potassium oxyzinate combined with carbon dots compound 180 was treated by intragastric administration,and the therapeutic effect was evaluated.Gomori results showed that benzbromarone and PD-CDs had therapeutic effects in the intervention treatment of gout models.In summary,this study investigated the function of carbon dots compound 180 in inducing hyperuricemia and gout in vivo and in vitro,and tested the therapeutic effects of AC-CDs and PD-CDs through gout models induced by carbon dots compounds.Carbon dots compound 180 combined with potassium oxyzinate can deposit uric acid after inhibiting the activity of uric acid oxidase to produce more uric acid,and produce uric acid salt precipitation or gout stones in the kidneys and joints.This internally simulates the pathogenesis of hyperuricemia and gout,providing a solid and stable animal model for the development and screening of new gout drugs.The therapeutic effect of PD-CDs in the intervention treatment of gout mice can provide a way for the development of new gout drugs.