【Animal Modeling】-Paeoniflorin improves Bayk8644-induced depression and anxiety-like behavior in rats and its mechanism

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

  Methods: 48 rats in normal group, L-type calcium channel agonist Bayk8644 group, paeoniflorin high-dose group, middle-dose group, low-dose group (200mg?Kgl?D', 100mg?Kg'?D', 50 mg? Kgl? is divided into d). '), the positive control nimodipine group (1 mg? Kgl? D'). The normal group and Bayk 8644 group received the same amount of 0.9?aCl solution, and the other groups received corresponding drug treatment. Except for the normal group, after 7 days of continuous administration, the other groups were intraperitoneally injected with Bayk8644 (0.2mg?Kgl?D'). The open field experiment and the elevated cross-maze experiment were used to evaluate the behavioral changes of rats, and the use of calmodulin-dependent protein kinase II (calmodulin-dependent protein kinase type II, CaMKII) and phosphorylated CaMKIIl (pho) using Western blotting . CaMKII) and brain-derived neurotrophic factor (BDNF).

  Results: Compared with the normal rat group, the Bayk 8644 group's total distance in the open field, time spent in the center, total distance in the center, and the number of upright objects were significantly reduced (Pu003c 0.05). or Pu003c0.01), The percentage of the frequency of rats entering the open arm (the percentage of OE time (OT significantly reduced (Pu003c0.05 or Pu003c0.01)), CaMKII, pho.-CaMKIII protein expression levels were significantly reduced (Pu003c0.05 or Pu003c0.01), BDNF protein The expression level was significantly reduced (Pu003c0.05). Compared with the Bayk8644 group, the paeoniflorin high- and medium-dose group had a longer total distance in the open field, and the number of columns increased significantly (Pu003c0.05). The high-dose paeoniflorin group was significantly Significantly prolonged (Pu003c0.05), the middle and low-dose group stayed in the central area significantly longer (Pu003c0.05) OE?OT? Pu003c0.05).u003c0.05)0.05 or Pu003c0.01) at high dose paeoniflorin OT? increased significantly in the CaMKII paeoniflorin group and the middle-dose paeoniflorin group (Pu003c0.05), and the CaMKII protein expression level in the CaMKII paeoniflorin high-dose group was significantly increased (Pu003c0.05), but significantly decreased (Pu003c0 .05 or Pu003c0.05). 01).

  Conclusion: Bayk8644 can cause depression and anxiety-like symptoms in rats, and paeoniflorin can antagonize the effect of Bayk8644. Paeoniflorin affects the activation of CaMKII protein by inhibiting L-type calcium channels, thereby exerting its pharmacological effects.