关键词: 睡眠剥夺, 五味子, 木脂素, Toll 样受体 4, 线粒体损伤

Abstract: Objective To explore the molecular mechanism by which Schisandra chinensis lignans (SCL) improve neuronal apoptosis and mitochondrial damage in the sleep deprivation (SD) model rats. Methods Forty-eight rats were divided into 6 groups: Control group, SD group, modafinil ( MOD) group ( positive control), and SCL treatment groups at different concentrations. The Morris water maze and Y-maze tests were used to assess the escape latency and behavioral accuracy of rats in each group, respectively. HE staining was used to detect hippocampal tissue pathological damage in rats, and TUNEL staining was used to detect cell apoptosis. JC-1 staining and ELISA were used to detect the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) in rats’brain tissues and cells. An in vitro neuronal damage model was established using the ROS inducer 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) to stimulate HT-22 cells. CCK-8 was used to measure cell viability. Western blotting was used to detect the expression levels of TLR4, MyD88, and p-NF-κB P65 in cells. Results Compared with those in the Control group, the escape latency of SD rats increased, and behavioral accuracy decreased. In contrast, rats treated with Mod or SCL showed reduced escape latency and increased behavioral accuracy (all P<0.05). Additionally, compared with rats in the Control group, rats in the SD group exhibited significant hippocampal tissue pathological damage, increased cell apoptosis, decreased MMP levels, and increased ROS levels. Mod or SCL intervention improved hippocampal tissue damage and cell apoptosis and reduced neuronal mitochondrial damage in SD rats (all P< 0. 05). Cellular experimental results showed that HT-22 cells in the DMNQ group had reduced viability, increased apoptosis, and increased mitochondrial damage and ROS levels when compared with those in the Control group. Mod or SCL treatment significantly improved the DMNQ-induced HT-22 cell damage. Moreover, compared with those in the Control group, the protein expression levels of TLR4, MyD88, and pNF-κB P65 in the DMNQ group cells were elevated, and Mod or SCL intervention significantly suppressed the levels of TLR4, MyD88, and p-NF-κB P65 in DMNQ-treated HT-22 cells. Conclusion SCL improves neuronal apoptosis and mitochondrial damage in SD rats by inhibiting the activation of the TLR4-MyD88-NF-κB pathway.

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