The Regulation To Expression Of Hx-heme-CD91 In Hematoma Clearance System After Intracerebral Hemorrhage By PPAR?-Nrf2 Pathway

Objective:After cerebral hemorrhage,peroxisome proliferator-activated receptor ?(PPAR?)activates the transcription factor nuclear factor-erythrocyte 2 p45-related factor 2(Nrf2),which regulates phagocytic-mediated endogenous hematoma clearance.After cerebral hemorrhage,free red blood cells are gradually degraded to hemoglobin(Hb),and then Hb is cleaved to form neurotoxic products such as heme,ferric iron,and free radicals,which cause secondary brain damage to surrounding brain tissue.Heme binds to hemopexin(Hx)to form Hx-heme complex,which is recognized by phagocytic surface scavenger receptor CD91,which forms Hx-heme-CD91 hematoma clearance pathway and mediates endocytosis of phagocytic cells.Studies have shown that the PPAR?-Nrf2 pathway can up-regulate the expression of CD36,scavenger receptor A(SRA),CD163 and other receptors on the surface of phagocytic cells,and promote the hematoma clearance process,but whether the PPAR?-Nrf2 pathway affects the expression of the Hx-heme-CD91 pathway has not been publicly reported.This topic aims to investigate the effect of PPAR?-Nrf2 on this pathway.Methods:Eighty-two male Sprague-Dawley(SD)rats were randomly divided into four groups: sham group(n=18),cerebral hemorrhage group(n=21),ICH+Monascin(PPAR?-Nrf2 agonist).Group(n=20),ICH+Gleevec(PPAR? inhibitor)group(n=23).Three days after surgery,all rats were scored for Modified Gorcia Score and then were randomly selected to measure brain water content,hemoglobin content.The expression levels of CD91 and Hx genes were determined by Western blot and real-time quantitative PCR(RT-q PCR).Results:Compared with the sham group,the Modified Gorcia Score,brain water content and hemoglobin content of the other groups were significantly increased,and the expression levels of CD91 and Hx genes were increased(p <0.05).Compared with the cerebral hemorrhage group,the Modified Gorcia Score was higher,the brain water content and hemoglobin content were significantly decreased,while the expression of CD91 and Hx was increased(p <0.05).The neurological function score was decreased and the brain water content was decreased in the Gleevec group.The hemoglobin content increased,and the expression levels of CD91 and Hx decreased(p<0.05).Conclusion:PPAR?-Nrf2 agonist monascus may enhance the hematoma clearance to reduce brain water content and hemoglobin content by up-regulating the Hx-heme-CD91 pathway,and exert neuroprotective effects.