催乳颗粒通过调控WTAP-Wnt5a-β-catenin信号轴改善溴隐亭诱导的大鼠产后缺乳OA

AIM:To study the effect and mecha-nism of Cuiru Keli(CRKL)on bromocriptine-induced postpartum hypogalactia in rats.METHODS:ELISA was used to detect the level of prolactin(PRL)in mammary tissue(MT)of postpartum hypogalactia.Cultivate rat mammary epithelial cells(RMECs)in vitro.The effect of CRKL on RMEC proliferation was detected by CCK8 method to determine the drug-containing serum.RT-qPCR and immunofluores-cence detection of lactose,milk fat,and milk pro-tein related gene expression.Network pharmacolo-gy predicts the signaling pathway of CRKL treat-ment for postpartum hypogalactia.Molecular dock-ing and molecular dynamics verification of the bind-ing between key components of CRKL and WTAP.RIP was used to study the interaction between WTAP and Wnt5a.RT-qPCR and Western blot were used to investigate the regulatory mechanism of CRKL on the Wnt/β-catenin signaling pathway.RE-SULTS:CRKL significantly increased the hourly milk production of female rats(P<0.05 or P<0.01).CRKL increases PRL levels in MT of model rats(P<0.01).Serum containing CRKL promotes the expression of PRLR,FASN,CSN2,and GLUT1(all P<0.05 or P<0.01).Network pharmacology predicts a high cor-relation between the Wnt/β-catenin signaling path-way and CRKL treatment for postpartum hypogalac-tia.And the serum containing CRKL promotes the expression of key genes CCND1,c-Myc,and β-catenin in the Wnt signaling pathway(all P<0.05 or P<0.01).Molecular docking and molecular dynam-ics indicate that the key component of CRKL has strong binding ability with WTAP.Overexpression of WTAP in RMECs interferes with the function of CRKL(P<0.01).CONCLUSION:CRKL improves bromocrip-tine-induced postpartum hypogalactia in rats through the WTAP-Wnt5a-β-catenin signaling axis.