动物造模 z-bio 2023-03-08 430

　　OBJECTIVE: To investigate the effects of K252a on rat behavior and classic depression-like indicators by microinjection of K252a into the hippocampus, and to establish a new animal model of depression.

　　Methods: SD rats were randomly divided into 5 groups, namely blank control group, sham operation group, chronic stress depression model group, intrahippocampal microinjection K252a group, and hippocampal microinjection K252a combined with chronic stress group. Open field experiment, sugar water consumption experiment and Morris water maze were used to determine the influence of rat behavior, ELISA method was used to detect the changes of serum monoamine transmitter content, and radioimmunoassay method was used to observe the changes of plasma CRH, ACTH and CORT content. Western blotting was used to observe the changes of BDNF, CREB, ERK1/2 and BCL-2 protein expression in rat hippocampus.

　　Results: Compared with the blank control group, the activity level, sugar water consumption, learning and memory ability of the rats in the CUMS group were significantly decreased (P<0.05 or P<0.01), HPA axis hyperfunction (P<0.01), serum monoamine transmitter The levels of BDNF, CREB, ERK1/2, and BCL-2 were down-regulated (P<0.01 or P<0.05), while there was no significant difference in the above indicators in the DMSO group. Compared with DMSO, the K252a group, In the K252a+CUMS group, the activity level, sugar water consumption, learning and memory ability decreased significantly (P<0.01 or P<0.05), the serum monoamine transmitter level decreased (P<0.01 or P<0.05), and the HPA axis function increased significantly (P<0.01 or P<0.05). <0.01 or P<0.05), the expressions of BDNF, CREB, ERK1/2, and BCL-2 in the hippocampus were significantly decreased (P<0.01 or P<0.05); compared with the CUMS group, the above indicators of the rats in the K252a group and K252a+CUMS group were significantly decreased (P<0.01 or P<0.05). There was no significant difference; compared with the K252a group, the above indexes of the K252a+CUMS group had no significant difference.

　　Conclusion: Analysis from different perspectives of behavior, hematology and molecular biology shows that this model has great similarity with the classic chronic stress depression model in terms of face validity, construct validity and functional validity, which can be used for Etiological studies and antidepressant drug screening provide an alternative research technology platform.