动物造模 z-bio 2022-01-04 908

　　Objective To explore the pharmacological mechanism of paeoniflorin in improving depression and anxiety-like behaviors in rats based on L-type voltage-dependent calcium channels.

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

　　Results Compared with 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 upright times were significantly reduced in the Bayk8644 group (P<0.05 or P<0.01), and the percentage of the number of times the rats entered the open arm (OE%) and time percentage (OT%) were significantly reduced (P<0.05 or P<0.01), CaMK Ⅱ, pho-CaMK ⅡI protein expression levels were significantly increased (P<0.05 or P<0.01), BDNF protein expression levels Significantly reduced (P<0.05). Compared with the Bayk8644 group, the total distance in the open field was prolonged in the high- and medium-dose groups of paeoniflorin, and the number of uprights was significantly increased (P<0.05). The total distance in the central area of the high-dose paeoniflorin group was significantly longer (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% of the high-dose paeoniflorin group (P<0.05 or P<0.01) and the OT% of the middle-dose paeoniflorin group were significantly increased ( P<0.05), the protein expression levels of CaMK II and pho-CaMK Ⅱ in rats in the high-dose paeoniflorin group were significantly reduced (P<0.05 or P<0.01), while the protein expression levels of BDNF were significantly increased (P<0.05).

　　Conclusion Bayk8644 can cause 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.