动物造模 z-bio 2022-11-30 541

　　Objective To investigate the pharmacological mechanism of paeoniflorin in improving depression-anxiety-like behavior in rats based on L-type voltage-dependent calcium channel.

　　Methods Forty-eight rats were divided into normal group, L-type calcium channel agonist Bayk8644 group, paeoniflorin high, medium and low dose groups (200mg·kgl·d', 100mg·kg'·d', 50mg·kgl·d' ), positive control nimodipine group (1 mg·kgl·d'). The normal group and the Bayk8644 group were given the same dose of 0.9% NaCl solution, and the other groups were given the corresponding drugs. After continuous administration for 7 days, except the normal group, the other groups were intraperitoneally injected with Bayk8644 (0.2 mg·kgl·d'). The behavioral changes of rats were evaluated by open field test and elevated plus maze test. Western blotting was used to detect calmodulin-dependent protein kinase type II (CaMK II) and phosphorylated CaMK IIl (pho-CaMK II) and brain-derived neurotrophic factor (brain-derived neurotrophic factor, BDNF) expression levels.

　　Results Compared with the rats in the normal group, the total distance in the open field, the stay time in the central area, the total distance in the central area and the number of standing uprights in the Bayk8644 group were significantly decreased (P<0.05 or P<0.01). (OE%) and time percentage (OT%) were significantly decreased (P<0.05 or P<0.01), the protein expression levels of CaMK II and pho-CaMK II II were significantly increased (P<0.05 or P<0.01), and the protein expression levels of BDNF were significantly increased (P<0.05 or P<0.01). significantly decreased (P<0.05). Compared with the Bayk8644 group, the total distance of the open field and the number of erections increased significantly in the paeoniflorin high-dose and medium-dose groups (P<0.05). The residence time in the central area of the middle and low dose groups was significantly prolonged (P<0.05), the OE% and OT% (P<0.05 or P<0.01) of the high-dose paeoniflorin group and the OT% of the middle-dose group of paeoniflorin were significantly increased (P<0.05 or P<0.01). P<0.05), the protein expression levels of CaMK II and pho-CaMK II in the high-dose paeoniflorin group were significantly decreased (P<0.05 or P<0.01), while the protein expression level of BDNF was significantly increased (P<0.05).

　　Conclusion Bayk8644 can induce depression and anxiety-like manifestations in rats, and paeoniflorin can antagonize the effect of Bayk8644. Paeoniflorin may affect the activation of CaMK II protein by inhibiting L-type calcium channels, thereby exerting its pharmacological effects.