[DJ-1 alleviates oxidative stress injury by activating the Nrf2 pathway in rats with cerebral ischemia-reperfusion injury].

OBJECTIVE To investigate the antioxidant effect of DJ-1 (Park7) in rats with cerebral ischemia/reperfusion (IR) injury and its potential mechanism. OBJECTIVE A total of 108 SD rats were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, Scramble group, DJ-1 siRNA group, negative control (NC) group and DJ-1 overexpression group. Except for those in the sham group, all the rats were subjected to MCAO to establish models of cerebral IR injury. In DJ-1 siRNA and DJ-1 overexpression group, a DJ-1 siRNA and an adeno-associated virus vector carrying DJ-1 gene was injected into the lateral ventricle of the rats, respectively. In each group, neurological scores and brain water content were determined after the operation, and pathological changes of the brain tissue and neuronal injury in the cortical infarction area were assessed using HE and Nissl staining. Oxidative stress in the brain tissues was analyzed by detecting superoxide dismutase (SOD) and malondialdehyde (MDA). The expression levels of DJ-1, Nrf2, Ho-1 and NQO1 in the brain tissue were detected with Western blotting, and the expression and nucleation of Nrf2 was determined by immunofluorescence staining. OBJECTIVE Compared with those in MCAO group, the neurological scores (P < 0.001) and brain water content (P < 0.001) were significantly increased in DJ-1 siRNA group. Intracerebral injection of DJ-1 siRNA following MCAO obviously aggravated neuron injury in cerebral ischemia region, further reduced SOD activity and increased MDA content (P < 0.001), and significantly lowered the expression levels of Nrf2 and its downstream proteins HO-1 and NQO1 (P < 0.001). Intracerebral injection of the adenoviral vector for DJ-1 (P=0.003) overexpression significantly upregulated the levels of Nrf2 (P=0.006) and its downstream proteins HO-1 (P=0.004) and NQO1 (P=0.014). OBJECTIVE As an important neuroprotective factor, DJ-1 alleviates oxidative stress induced by cerebral IR injury in rats by activating the Nrf2 pathway.