The Neuroprotective Effect and Mechanism of Geniposide on Diabetes Complicated with Depression Model Rats Based on Sirt1/Nrf2/HO-1/Gpx4 Axis
NIE Wei1, JIANG Yuwei2, YANG Li1, ZHANG Yang1*
This study aims to investigate the neuroprotective effects and mechanisms of GNP (geniposide) on DD (diabetes complicated with depression) model rats based on the Sirt1/Nrf2/HO-1/Gpx4 (silentin forma tion regulators 1/nuclear factor E2-related factor 2/heme oxygenase-1/glutathione peroxidase 4) axis. Seventy two, 8-week-old, SD male rats (12 rats per group) were divided into Ctrl group (control group), DD group (model group), L-GNP group (model+low-dose GNP group), M-GNP group (model+medium-dose GNP group), H-GNP group (model+high-dose GNP group), and H-GNP+EX527 group (model+high-dose GNP+Sirt1 specific inhibitor group). The blood glucose meter was used to detect FBG (fasting blood glucose) in rats. The forced swimming ex periment and tail suspension experiment were used to detect rat behaviors. The ELISA method was used to detectserum inflammatory factors, oxidative stress, neurotransmitters in hippocampal tissue, and BDNF levels. HE stain ing and Nissl staining were performed to observe pathological changes in hippocampal tissue. Transmission micro scope was performed to observe mitochondrial morphology. Western blot was used to detect the Sirt1, Nrf2, HO-1, Gpx4 and ACSL4 proteins in hippocampal tissue. Compared with the DD group, GNP effectively alleviated the the disorder of neuronal arrangement, cell body swelling, nuclear condensation, and mitochondrial structural damage, while the levels of FBG were decreased; the time of forced swimming and tail suspension was shotende; the levels of serum pro-inflammatory factors (TNF-α, IL-1β), oxidative damage products (MDA, Fe²⁺), and ACSL4 protein expression were significantly decreased (P<0.05), while the levels of antioxidant enzyme (GSH-PX, SOD) activity, neurotransmitter and neurotrophic factor (DA, 5-HT, NE, BDNF) and Sirt1, Nrf2, HO-1, Gpx4 protein expression levels were significantly inceased (P<0.05). GNP may have a protective effect on the nerves of DD rats by activat ing the Sirt1/Nrf2/HO-1/Gpx4 axis.
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