动物造模 z-bio 2022-07-21 282

　　Objective: To observe the expression changes of Ghrelin on DKK-1 and WNT signaling pathways in diabetic rats, and to explore the mechanism involved in learning and memory function.

　　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) . The rat model of diabetes was established by intraperitoneal injection of STZ (60 mg/kg), and the spatial learning and memory abilities of the rats were detected by Morris water maze test; the ultrastructure of the CA1 area of the hippocampus of the rats was observed by electron microscope, and the CA1 area of the hippocampus of the rats was observed by HE staining under a common microscope. Cell morphology; serum DKK-1 expression was detected by ELISA; mRNA and protein levels of DKK-1 and β-catenin in rat hippocampus were detected by fluorescence quantitative PCR and Western blotting, respectively.

　　Results: Compared with the NC group, the escape latency of the DM group was prolonged, and the number of crossing the platform was reduced (P<0.05); neuronal cells were swollen, mitochondrial vacuolar degeneration, etc. (P<0.05); The expression of DKK-1 in serum and hippocampus was significantly increased (P<0.05), and the expression of β-catenin in hippocampus was decreased (P<0.05). Compared with the DM group, the escape latency of the rats in the DM1 group was shortened, and the number of crossing the platform increased (P<0.05); the neuron cells were morphologically intact, the mitochondria were developed, and the density was increased (P<0.05); The expression of DKK-1 in serum and hippocampus was significantly decreased (P<0.05), and the expression of β-catenin in hippocampus was increased (P<0.05). The above-mentioned effects of Ghrelin were blocked after combined application of Ghrelin and GHSR-1a receptor antagonist Ghrelin+D-lys3-GHRP-6 (P<0.05).

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