动物造模,抑郁焦虑 z-bio 2022-12-14 398

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

　　Methods Forty eight rats were divided into normal group, Bayk 8644, a L-type calcium channel agonist, high, medium and low dose paeoniflorin groups (200mg · kg · d ', 100mg · kg' · d ', 50mg · kg · d'), and positive control group (1mg · kg · d '). The normal group and Bayk8644 group were given 0.9% NaCl solution of the same dose, and the other groups were given corresponding drugs. After 7 days of continuous administration, Bayk8644 (0.2 mg · kgl · d ') was intraperitoneally injected into other groups except the normal group. The behavioral changes of rats were evaluated by open field test and elevated cross maze test. The expression levels of calmodulin dependent protein kinase type Ⅱ (CaMK Ⅱ), phosphorylated CaMK Ⅱ l (photo CaMK Ⅱ) and brain-derived neurotrophic factor (BDNF) in hippocampus were detected by Western blot.

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

　　Conclusion Bayk8644 can cause depression and anxiety in rats, and paeoniflorin can antagonize the effect of Bayk8644. Paeoniflorin may affect the activation of CaMK Ⅱ protein by inhibiting L-type calcium channel, so as to play its pharmacological role.