动物实验,糖尿病 z-bo 2020-08-22 482

　　OBJECTIVE: To observe the expression changes of Ghrelin on DKK-1 and WNT signaling pathways in diabetic rats, and to explore the mechanism of its involvement in learning and memory functions.

　　Methods: 60 SD rats were randomly divided into control group (NC group), diabetes group (DM group), diabetes + Ghrelin group (DM1 group), diabetes + Ghrelin + D-lys3-GHRP-6 group (DM2 group) . Intraperitoneal injection of STZ (60 mg/kg) to establish a diabetic rat model, Morris water maze test to detect the spatial learning and memory ability of rats; electron microscopy to observe the ultrastructure of the rat hippocampus CA1 area, and HE staining to observe the rat hippocampus CA1 area under a common microscope Cell morphology; ELISA to detect the expression of rat serum DKK-1; fluorescence quantitative PCR and Western blotting to detect the mRNA and protein levels of rat hippocampus DKK-1 and β-catenin, respectively.

　　Results: Compared with the NC group, rats in the DM group had longer escape latency and reduced the number of crossing platforms (P<0.05); neuronal cell swelling, mitochondrial vacuole degeneration, etc. (P<0.05); neuronal cell arrangement disorder, cell nucleus The expression of DKK-1 in serum and hippocampus was significantly increased (P<0.05), and the expression of β-catenin in the hippocampus decreased (P<0.05). Compared with the DM group, rats in the DM1 group had a shorter escape latency and increased the number of crossing platforms (P<0.05); neuronal cells had complete morphology, developed mitochondria, and increased density (P<0.05); neuronal cells were arranged neatly and cell layers The numbers are clear; the expression of DKK-1 in serum and hippocampus tissue was significantly reduced (P<0.05), and the expression of β-catenin in the hippocampus increased (P<0.05). After combined application of Ghrelin and the GHSR-1a receptor antagonist Ghrelin+D-lys3-GHRP-6, the above effects of Ghrelin were blocked (P<0.05).

　　Conclusion: The WNT signaling pathway may be involved in the occurrence and development of diabetic encephalopathy. The mechanism of Ghrelin improving the learning and memory function of diabetic rats is at least partly related to down-regulating the expression of hippocampal DKK-1 and regulating the WNT signaling pathway.