To explore the role of heme-hemopexin-low density lipoprotein receptor related protein 1 (LRP1) pathway in hematoma clearance followed intracerebral hemorrhage (ICH) as well as its regulatory mechanism of peroxisome proliferator-activated receptor γ (PPAR-γ)/nuclear factor-erythroid 2 related factor-2 (Nrf2).

ICH was induced by stereotactic, intrastriatal injection of type Ⅳ collagenase. 86 male SD rats were randomly divided into sham, ICH+vehicle (normal saline), ICH+monascin (dual PPAR-γ/Nrf2 agonist, 10 mg/kg, twice daily), ICH+gleevec (PPAR-γ antagonist, 100 mg/kg, once a day). Monascin and gleevec were administered by gastric perfusion for 3 days after ICH induction. Hematoma volume and brain edema were assayed by brain magnetic resonance imaging (MRI), and hemoglobin levels and brain water content were evaluated at 3 days after ICH. Brain expression of Hx/LRP1 with microglia were analyzed by double-labelling immunofluorescence and western blot. One-way analysis of variance (ANOVA) was performed for comparisons among multiple groups, and Tukey's test was used for pairwise comparison between groups. The correlation between hematoma and hemoglobin content, edema and cerebral water content were analyzed by Pearson correlation.

Hematoma volume and brain edema assessed by MRI as well as hemoglobin levels and brain water content showed which were reduced in monascin-treated ICH while increased in gleevec-treated ICH; Expression of LRP1 and Hx on microglia were significantly increased after ICH, especially expressed around vessels in monascin-treated ICH. Pearson correlation analysis revealed that there was a positive correlation between edema volume shown by MRI and brain water content (r=0.956, P=0.005), hematoma volume as shown by MRI and brain hemoglobin levels (r=0.924，P=0.010).

As a PPAR-γ/Nrf2 dual-target agonist，monascin promoted hematoma removal through inducing LRP1 and Hx expressed on microglia around vessels, while alleviating secondary edema formation followed ICH; It showed that PPAR-γ/Nrf2 participates in hematoma removal after ICH by regulating Heme-Hx-LRP1 pathway; The determination of hematoma and edema by MRI was consistent with the detection of hemoglobin and brain water content in brain tissue.