Previous studies have demonstrated that specific activation or overexpression of Nrf2 or HO-1 ameliorated PIHF(Ma et al. 2019; Bubb et al. 2017; Wang et al. 2010), and on the other hand, Pino could focus on Nrf2/ARE pathway to exert protective effects on depression (Wang et al. 2020), neurotoxicity (Jin et al. 2015), etc., with the interaction undefined in a PIHF model. Here, NFE2L2 is linked to depressive disorder.