Abstract: Objective To investigate the effect of nuclear factor E2 related factor 2 (Nrf2) on cerebral ischemiareperfusion injury and the regulation of melanoma deficiency factor 2 (AIM2) inflammatory bodies. Methods A total of 108 male SD rats were divided into the sham group, the cerebral ischemia-reperfusion group (I/R group) and the Brucitol intervention group (Bru group) according to random number table. Each group was further divided into 3 groups at 8 h, 24 h and 72 h after cerebral ischemia-reperfusion with 12 rats in each group according to random number table. Middle cerebral artery occlusion (MCAO) model was established by using the the Longa method in the I/R group and the Bru group. The neurological deficits were scored at the corresponding time points. The area of cerebral infarction was detected by 2, 3, 5- triphenyltetrazolium chloride (TTC). The brain tissues injury was detected by HE staining. qPCR was used to detect expression of AIM2 mRNA in brain tissue on the ischemic side. Western blot assay was used to detect the expression levels of AIM2 and Nrf2 proteins in ischemic brain tissue. The expressions of apoptosis-related speck-like protein (ASC), Caspase- 1, interleukin (IL) -1β and IL-18 in ischemic brain tissue were detected by ELISA. Results Compared with the sham group, neurological deficit score at each time point in the I/R group was increased (P＜0.05), and pathological injury of brain tissue was significantly aggravated. AIM2 mRNA, the protein expression levels of Nrf2, AIM2, ASC, Caspase-1, IL-1β and IL-18 were increased in the I/R group (P＜0.05). Compared with the I/R group, the neurological deficit score was higher at each time point in the Bru group, and the cerebral infarction area was larger (P＜0.05). There were more severe pathological damage of brain tissue, lower Nrf2 protein expression level. AIM2 mRNA and protein was higher, and cerebral infarction area was higher (P＜0.05), the protein expression levels of ASC, Caspase-1, IL-1β and IL-18 increased (P＜ 0.05). Conclusion Nrf2 plays an endogenous neuroprotective role in cerebral ischemia-reperfusion injury, and the mechanism may be related to Nrf2 negatively regulating AIM2 inflammasome and reducing the release of pro-inflammatory cytokines.

Key words: brain ischemia, reperfusion injury, inflammation, NF-E2-related factor 2, absent in melanoma 2