Abstract:Objective To investigate the effect oforexin receptor 1(OX1R)antisensephosphorothioate-oligodeoxynucleotides (OX1R-PS-ASODNs) on the metabolism of blood glucoseand insulinand the expression of OX1R protein in hypothalamus of obese rats. Methods Obese model induced by high-fat diet was established in 40 rats (obesity group), and the obese model was successfully established in 37 rats. Ten rats fed ordinary feed were served as normal control group. Twenty-four rats of 32 obese rats were randomly divided into antisense group, mismatch group, saline group and control group (n=8 each). Except for control group, OX1R antisense and mismatch phosphorothioate-oligodeoxynucleotides (PS-ODNs) and normal saline were respectively given via intracerebroventricular intubation injection in the other 3 groups. Mini glucometer was used to detect blood glucose. Chemiluminescence immunoassay (DPC corporation analyzer) was used to detect serum insulin. Immunohistochemical assay was used to analyze the expression of OX1R protein in hypothalamus. Results Compared with normal control group, body weight, Lee's index and the expression of OX1R protein in hypothalamus in obesity group increased significantly (P<0.01, P<0.05). After intracerebroventricular injection of OX1R-PS-ASODNs, OX1R protein expression level decreased, and the levels of blood glucose and insulin declined in obesity group compared with control group, mismatch group and saline group (all P<0.01). Conclusion OX1R is associated with nutritional obesity and participates in energy balance and metabolic regulation, while OX1R-PS-ASODNs can decrease the expression of OX1R protein in hypothalamus and improve blood glucose and insulin levels for the nutritional obesity rats.