芒柄花素逆转多柔比星诱导的乳腺癌荷瘤小鼠胸腺输出功能降低OA

Objective:This paper aims to investigate the reversing effect of formononetin on doxorubicin(DOX)-in-duced reduction of thymic output function in breast cancer-bearing mice.Methods:A mouse model of impaired thymic T-cell output function was established by intraperitoneal injection of DOX.Formononetin intervention was performed via subcutaneous injection at the Tiantu acupoint(RN22)once daily for consecutive 14 days.Mice were divided into a nor-mal control group,a model control group,and a 5 mg/kg formononetin group.General appearance,body weight,and hair growth of mice were observed,and the thymic index was calculated.Hematoxylin-eosin(HE)staining was used to evalu-ate thymic tissue structure,and flow cytometry was performed to detect the proportions of thymic T-cell subsets.Addition-ally,thymic tissues from breast cancer-bearing mice were collected for in vitro culture.After DOX intervention,the tis-sues were treated with different doses of formononetin(0.01,0.1,1,and 10 μmol/L).HE staining was used to observe the morphology of isolated thymic tissues,and immunofluorescence was employed to label Cytokeratin 5(CK5)and CK8 positive cells,thereby observing the distribution and morphology of thymic epithelial cells.Results:Compared with those in the normal control group,mice in the model control group exhibited rough hair,decreased mobility,reduced body weight,thinning of the thymic cortex,decreased density of cortical thymocytes,and blurred corticomedullary junction.The percentage of double-positive(CD3+CD4+CD8+)cells was increased,while the percentage of mature CD8+single-posi-tive(CD3+CD4-CD8+)cells was decreased(P＜0.05).Compared with the model control group,the formononetin-trea-ted group showed smooth hair,restored mobility,and partial recovery of thymic cortical thickness,thymocyte density,and corticomedullary demarcation.Notably,the percentage of double-positive(CD3+CD4+CD8+)cells was significantly re-duced(P＜0.01).In vitro organ experiments showed that formononetin restored the inhibition of proliferation and differ-entiation of cells in DOX-induced isolated thymic tissues and upregulated the positive expressions of CK5 and CK8 in thymic tissues.Conclusion:Formononetin can protect DOX-induced thymic tissue injury in mice,increase the number of thymic epithelial cells,and regulate thymic output function,which may exhibit a role in promoting central immune recon-stitution after chemotherapy.