ABSTRACT
Sepsis is a life-threatening organ dysfunction caused by the disorder of the body's response to infection, and is one of the main causes of death in critically ill patients. Ferroptosis is a kind of iron dependent cell death, characterized by intracellular reactive oxygen species (ROS) accumulation. Sepsis can cause a substantial accumulation of ROS in cells. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant and plays a critical protective role in sepsis induced ferroptosis by regulating the expression of proteins related to the ferroptosis pathway. Current studies have found that activation of Nrf2 has a protective effect on ferroptosis induced by sepsis. In this paper, we summarized the regulation mechanism of Nrf2 in ferroptosis, in order to provide references for the treatment of sepsis.
ABSTRACT
BACKGROUND: Tonifying kidney is the main method to treat aging of nervous system, which is characterized by decreasing density of nerve cells,cell aging and deposition of lipofuscin granule in the cytoplasm of nerve cell.OBJECTIVE: To investigate the effect of nourishing kidney and tonifying brain on density and ultrastructural of nerve cell in hippocampal CA1 and CA3 area of aging mouse. DESIGN: Completely randomized and controlled study.SETTING: Institute of Traditional Chinese Medicine of Hunan Province.MATERIALS: The experiment was completed at the Pharmacological Laboratory of Institute of Traditional Chinese Medicine of Hunan Province between September 2000 and November 2003. Totally 30 Kunming mice with 11-month old were selected. Solution of yishen jiannao Ⅰ (zishen prescription) was provided by Agent Laboratory of Institute of Traditional Chinese Medicine of Hunan Province (including 15 g shouwu, 15 g sangshen, 15 g gouqizi, 6 g wuweizi, 30 g danshen, 30 g gegen, 10 g honghua,10 g shichangpu, 10 g yujin, 10 g yuanzhi, 10 g shanzha and scorpion).Scorpion was crushed into power. The rest drugs were decocted with water twice, mixed together and filtered, then the powder of scropion was added.The raw material was 1.0 g/mL.METHODS: Thirty mice were randomly divided into 3 groups with 10 in each group. Mice in control group were given distilled water, those in zishen prescription group were given 20.0 g/kg zishen prescription, and in vitamin E group were given 40.0 mg/kg vitamin E. All mice were perfused with 20 mL/g, once a day for 4 weeks. After 1 hour of the last medication, mice were sacrificed at once at the drugged state. Cranium of mice was sheared and the hippocampal tissue was taken out. Numbers of nerve cells in CA1 and CA3 area were calculated under the microscope to calculate the density of nerve cell.MAIN OUTCOME MEASURES: ① Density of nerve cell in cerebral hippocampus of mice in each group; ② Ultrastructure of nerve cell in cerebral hippocamp us of mice in each group.RESULTS: Totally 30 mice entered the final analysis. ① Density of nerve cell in hippocampal CA1 and CA3 area of brain: Density in zishen prescription group and vitamin E group was higher than that in control group [CA1: (3 707±495), (3 812±281), (257±372) mm-2; CA3:(2 746±262),(2 397±366), (1 992±307) mm-2, t=2.68-8.30, P ＜ 0.05-0.01]. ② Aging of mitochondrion was decreased, deposition of lipofuscin and aging of lysosome in cytoplasm were reduced in zishen prescription group and vitamin E group.CONCLUSION: Granule of nourishing kidney and tonifying brain can defer density decrease of nerve cell and aging of cell in hippocampla area of mice' brain.