Role of Nrf2 signaling pathway in hydrogen sulfide-induced inhibition of inflammatory responses in brain tissues of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway in hydrogen sulfide (H 2S)-induced inhibition of inflammatory responses in the brain tissues of mice with sepsis-associated encephalopathy (SAE). Methods:Fifty-four wild-type C57BL/6J mice and thirty-six Nrf2 -/-C57BL/6J mice, weighing 20-25 g, were divided into 5 groups ( n=18 each) using a random number table method: wild-type sham operation group (wild-type Sham group), wild-type SAE group, wild-type SAE+ NaHS group, Nrf2 -/-SAE group, and Nrf2 -/-SAE+ NaHS group.After the model of SAE was established by cecal ligation and puncture in anesthetized mice.NaHS 50 μmol/kg was intraperitoneally injected at 3 h after the model was successfully established.The mice were sacrificed at 24 h after surgery, and brain tissues were obtained for examination of the phathological changes and for determination of the number of viable neurons, the expression of NLRP3 (by Western blot), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay), and percentage of Iba-1 + CD86 + , Iba-1 + CD206 + and Iba-1 + cells (by flow cytometry). Results:Compared with wild-type Sham group, NLRP3 expression was significantly up-regulated, contents of TNF-α, IL-1β and IL-6 and percentage of Iba-1 + CD86 + and Iba-1 + cells were increased, and the percentage of Iba-1 + CD206 + cells and neuron survival rate were decreased in wild-type SAE group ( P<0.05). Compared with wild-type SAE group, NLRP3 expression was significantly down-regulated, contents of TNF-α, IL-1β and IL-6, percentage of Iba-1 + and Iba-1 + CD86 + and neuron survival rate were decreased, and the percentage of Iba-1 + CD206 + cells was increased in wild-type SAE+ NaHS group ( P<0.05). There was no significant difference in each parameter between Nrf2 -/-SAE group and Nrf2 -/-SAE+ NaHS group ( P>0.05). Compared with wild-type SAE+ NaHS group, NLRP3 expression was significantly up-regulated, the percentage of Iba-1 + and Iba-1 + CD86 + and contents of TNF-α, IL-1β and IL-6 were increased, and the percentage of Iba-1 + CD86 + cells and neuron survival rate were decreased in Nrf2 -/-SAE+ NaHS group ( P<0.05). Conclusion:Nrf2 signaling pathway is involved in H 2S-induced inhibition of inflammatory responses in the brain tissues of mice with SAE.