动物造模 z-bio 2022-12-14 408

　　Objective To study the morphological and functional changes of microglia in rat brain after leptin receptor (LEPR) gene knockout, and explore the function of leptin receptor in microglia.

　　Methods RT-PCR, Western blot, immunohistochemistry and immunofluorescence were used to observe the activation of microglia in vitro and in vivo after leptin receptor knockout in rats.

　　Results Leptin receptor was expressed in microglia, and gene knockout could completely eliminate the LEPR protein in microglia; LEPR knockout enhanced the inflammatory response of LPS to stimulation in rats, and the survival rate decreased by 75%; The proportion of activated microglia in the brain of LEPR knockout rats increased significantly; The primary microglia knocked out by LEPR not only secreted more inflammatory factors, but also enhanced phagocytosis; Western blot showed that the phosphorylation of PI3K/AKT was significantly enhanced in the brain protein of leptin receptor knockout rats.

　　Conclusion After leptin receptor knockout, rat microglia develop towards the direction of promoting inflammation and phagocytosis, revealing that LEPR/Leptin may regulate neuroinflammation through microglia.