Nrf2 deficiency promotes microgila/macrophage activation after subarachno id hemorrhage in mice / 医学研究生学报

ABSTRACT

Objective Subarachnoid hemorrhage ( SAH) is a devastating disease with high fatality and morbidity and micro-glia/macrophage ( M/M) plays a vital role in SAH brain injury with complicated pathophysiological mechanism .This study was to ob-serve the effect of Nrf2 deficiency on M/M activation and M1 polarization after subarachnoid hemorrhage in mice . Meth ods We col-lected 70 wild-type ( WT) ICR mice and 35 Nrf2-knockout ( KO) mice to establish the SAH model by injecting fresh autologous blood into pre-chiasmatic cistern.WT mice were arranged into four groups sham operation group, post operative day 1 (POD1) group, POD3 group and POD5 group.Then WT mice and Nrf2 Nrf2-knockout mice were divided into sham operation WT group , sham opera-tion KO group, SAH WT group and SAH KO group.Western blotting (WB) and immunohistochemistry (IHC) were applied to observe the activation and proliferation of M/M after SAH on WT mice .Difference in activation and M 1 polarization were observed by detecting Iba1 expression in WB and CD 16/32 +Iba1 +cells in immunofluorescence between WT and KO mice . Results Gray scale values of Iba1 expression by WB in WT mice are 0.491 ±0.039, 0.657 ± 0.069, 0.930 ±0.046 and 0.926 ±0.046;average optical intensity values of Iba1 expression by IHC in WT mice are 0.412 ±0.122, 0.625 ±0.135, 0.963 ±0.213 and 0.978 ±0.224.The data indica-ted that Iba1 expression increased in SAH KO group in comparison to SAH WT group on 1, 3, 5 day after SAH (P<0.05).Moreover, Nrf2 deficiency promoted the activation and polarization of M /M by increased Iba1 protein expression and CD16/32 +Iba1 +cells after SAH ( P<0.05). Conclusion SAH induces M/M activation and proliferation in mice, and Nrf2 deficiency promotes the activa-tion, proliferation and M1 polarization after SAH .