The Regulation To The Expression Of CD36 And SRA Through PPARγ-Nrf2 Pathway In Hematoma Scavenging After Intracerebral Hemorrhage

Objective:CD36 is one of the recognized brain scavenger receptors and mediates the phagocytosis and clearance of apoptotic and damaged cells including red blood cells.SRA(scavenger receptor class A)is a pattern recognition receptor mainly expressed on microglia/macrophages.It can directly affect the activity of microglia/macrophages and participate in the phagocytosis and clearance of bacteria and amyloid.The mechanism of CD36 and SRA in hematoma elimination after intracerebral hemorrhage(ICH)is still unclear.Peroxisome proliferator-activated receptor gamma(PPARγ)and nuclear factor-E2 related factor2(Nrf2)have attracted attention in the regulation of phagocytic cell-mediated endogenous hematoma clearance,and may play a role by affecting the expression of CD36 and SRA.This study intends to observe the natural expression of CD36 and SRA after ICH by comparing sham group and vehicle group,and explore the regulatory mechanism of the PPARγ-Nrf2 pathway on the scavenger receptors CD36 and SRA after ICH by regulating the PPARγ-Nrf2 pathway of the endogenous hematoma clearance.Methods:163 male Sprague-Dawley(SD)rats were randomly assigned as sham group,vehicle group;ICH + Gleevec(PPARγ inhibitor)group,ICH + Monascin(PPARγ-Nrf2 agonist)group and ICH + Fucoidan(SRA agonist)group.ICH model was induced by type IV collagenase and the sham group was injected with the same amount of saline.Experimental groups were immediately given the drug via gavage after ICH.The sham group and vehicle group were given the same amount of saline.After ICH 3 days,neurological deficit scores were performed,brain water content and hemoglobin assay were measured.Head magnetic resonance imaging(MRI)was performed to measure the volume of hematoma and the volume of edema around the hematoma.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to determine the expression of Nrf2,CD36,and SRA.Results:Compared with sham group,the neurological impairment was significant in all ICH rats.Brain water content,hemoglobin assay,hematoma volume and edema volume increased significantly,and the expression of Nrf2,CD36,SRA increased(p < 0.05).Compared with vehicle group,neurological deficit scores were higher in ICH + Monascin group and ICH + Fucoidan group.Brain water content,hemoglobin assay,hematoma volume and edema volume were significantly decreased,while Nrf2,CD36,and SRA were highly expressed(p<0.05).Compared with vehicle group,neurological deficit scores were lower in ICH+Gleevec group.Brain water content,hemoglobin assay,hematoma volume and edema volume were increased slightly,and Nrf2,CD36,and SRA were lower expression(p<0.05).Conclusion:CD36 and SRA may play an important role in the endogenous hematoma clearance system after cerebral hemorrhage.Monascin may promote hematoma clearance,reduce cerebral edema,and play a neuroprotective role by activating PPARγ-Nrf2-CD36 and PPARγ-Nrf2-SRA pathways.