HS Alleviates Propofol-Induced Impaired Learning and Memory by Promoting Nuclear Translocation of and Inhibiting Apoptosis and Pyroptosis in Hippocampal Neurons.

Background: Repeated exposure to propofol can affect their learning and memory functions, but the mechanism remains unclear. The current study aimed to investigate the mechanism underlying the effect of hydrogen sulfide (HS) on the alleviation of propofol-induced learning and memory impairment, mediated by promoting nuclear translocation of the nuclear factor erythroid 2-related factor 2 () and inhibiting apoptosis and pyroptosis in hippocampal neurons.

Methods: Rats used in this study were successively exposed to 200 mg/kg propofol for 8 consecutive weeks, followed by inhalation of 10, 40 or 80 ppm HS. Subsequently, the effects of different concentrations of HS on learning and memory were assessed using the water maze assay. Additionally, the effects of HS on cell apoptosis and pyroptosis and nuclear translocation of in hippocampal neurons were also determined. Furthermore, NaHS (200 μmol/L) was used as an donor for HS, and rescue experiments were carried out following knockdown in H19-7 cells. Moreover, function was inhibited following treatment with an intraperitoneal injection of ML385 (30 mg/kg) in the rats. The effects of HS on reactive oxygen species (ROS) generation, cell apoptosis, and pyroptosis in propofol-treated and -deficient H19-7 cells were also investigated.

Results: Exposure to propofol for 8 weeks affected the ability of the rats to find underwater platforms ( < 0.01). Further, the exposure induced cell apoptosis and NLR family pyrin domain containing 3 (NLRP3)-related pyroptosis ( < 0.01). Although inhalation of 10 ppm HS did not attenuate the aforementioned effects ( > 0.05), exposure to 40 and 80 ppm HS significantly alleviated propofol-induced injury in the hippocampal neurons ( < 0.01). However, the protective effect of 80 ppm HS was more obvious as compared to that of the other two doses ( < 0.01). In addition, knockdown aggravated the propofol-induced cell pyroptosis and apoptosis as well as reversed the protective effect of HS against these processes ( < 0.01). experiments in this study demonstrated that inhibition abrogated the protective effects of HS inhalation against learning and memory impairment as well as propofol-induced cell apoptosis and pyroptosis in rats ( < 0.01).

Conclusions: HS could attenuate propofol-induced damage in hippocampal neurons by promoting the nuclear translocation of and inhibiting cell apoptosis and pyroptosis.