Establishment Of Rat Heterotopic Cardiac Allotransplantation Model And Study On The Effect Of Daphnetin On Postoperative Anti-Immune Rejection

Immunosuppressive drugs are an important class of drugs that are clinically used to treat autoimmune diseases and transplant rejection.They have a good application value in the treatment of human diseases.Organ transplantation has become an extremely common treatment,but its postoperative immunological rejection has become a key factor in the success of transplantation.In recent years,studies have shown that Daphnetin has an immunosuppressive effect on lymphocytes,but no experiment has demonstrated its inhibitory effect on immune rejection from the perspective of regulatory T cells.Therefore,in this study,xenotypic intraperitoneal heterotopic transplantation was used as a model for postoperative treatment with daphnetin.The immunosuppressive effect of daphnetin was investigated by examining the expression level of regulatory T cells after surgery.This opens up new directions for immunosuppressant drugs,providing a theoretical basis and application basis for the treatment of immune rejection and autoimmune diseases after organ transplantation.Daphnetin DAP is a dihydroxyl derivative of coumarin derived from plants and is an effective compound extracted from a plant named L.regale.Daphnetin is known for its antithrombotic,anti-inflammatory and antioxidant activities.It has been used clinically for the treatment of coagulopathy,rheumatoid arthritis,low back pain,and fever.In addition,Daphnetin exhibits a significant anti-cancer effect in vitro and inhibits kinase activity.Daphnetin is also capable of producing significant anti-proliferative activity in different malignant cell lines.These findings indicate that daphnetin has potential immunosuppressive functions.In this experiment,a heterotopic cardiac allograft model was used in rats.Wistar rats and SD rats were selected as experimental animals.15 donor Wistar rats and 15 recipient SD rats were randomly divided into 3 groups.In group A,daphnetin4 mg/kg was intraperitoneally injected 12 hours before and after surgery.Samples were collected 5 days and 7 days after surgery.Group B received intraperitoneal injection of cyclosporine 10 mg/kg 12 hours before and after surgery.Samples were taken at 5d and 7d.In group C,normal saline was injected intraperitoneally 12 hours before and after surgery.Samples were collected 5 days and 7 days after surgery.Postoperatively,the rats'mental status was observed and hematological tests were performed.Peripheral blood and spleen were collected on the 5th and 7th days after operation.The levels of CD4~+CD25~+Treg cells,Foxp3 gene and IL-10 were measured.The experimental results showed that daphnetin was injected intraperitoneally for8 days at a dose of 4 mg/kg,which did not cause liver and kidney damage in rats and had some anti-inflammatory effects.Daphnetin can increase the content of CD4~+CD25~+Foxp3~+Treg cells in rats after organ transplantation,thus playing an anti-immune rejection effect.Compared to cyclosporine A,which is commonly used clinically,Daphnetin has the advantages of fewer side effects and can increase the content of CD4~+CD25~+Foxp3~+Treg cells.