The Effect Of Baishile Capsule On Hippocampus Nerve Regeneration Of Chronic Unpredicted Mild Stress Depression Model Rats By Signal Pathway Of CAMP-CREB-BDNF

Objective:To investigate Baishile (BSL) capsule on behavior, hippocampal neurogenesis in chronic unpredicted mile stress (CUMS) depression model rats, study the molecular mechanism of signal pathway of cAMP-CREB-BDNF in CUMS rats, explore the intracellular signal transduction mechanisms and targets.Method:SD rats were randomly divided into control group, sham operation, CUMS, fluoxetine (5.4mg/kg), BSL group, BSL capsule+K252a, K252a group. Fluoxetine and BSL group were i.g. for21consecutive days; K252a group hippocampal microinjected K252a once a week; BSL capsule+K252a group i.g. and given once a week K252a microinjected into hippocampus. Body weight change of rats, Open-field,1%sucrose, Morris water maze, adrenal cortex were carried out to observe behavioral changes at21d. Observe CA3and DG of hippocampal neurons pathological change by HE staining. The protein expression of PKA, BDNF, CREB were detected by immunohistochemical; PKA, BDNF, CREB were detected by Wesern-blotting; BDNF, CREB mRNA expression were detected by Realtime-PCR.Results:Behavior changes of CUMS ras:Compared with model group, fluoxetine and BSL Capsule group could increase body weight change, sucrose partial eclipse degree, horizontal and vertical number of activities at21days(p<0.01or p<0.05), shorten EL, latency of the target quadrant(p<0.05); microinjection of K252a in hippocampus showed symptoms similar to the CUMS group, compared with the sham group, the K252a body weight change, sucrose water partial eclipse degree, activity and rearing, crossing the target quadrant was significantly decreased(p<0.01), EL was increased(p<0.05), the difference was not statistically significant with the model group. Compared with the K252a group, BSL Capsule+K252a group coule change depressed like behavior, but it had no dfifference.②ompared with the model group, the BSL Capsule group and fluoxetine group, CA3neurons arranged in neat rows, most of the neurons in the nucleus, nuclear membrane structure more clearly, Nissl bodies increased, cytoplasmic concentrated deeply stained reduce; the number of granule cells increased close and orderly arrangement in DG Compared with the sham group, K252a group exist hippocampus pathological changes clearly in CA3, DG area, cell number was significantly reduced and the presence of atrophy, the extent of the damage is more severe compared with the model group.③rotein detection:Compared with control,sham group, the expression of PKA, BDNF, CREB in hippocampal decreased in model group rat (p<0.01or p<0.05); Compared with the model group, the BSL capsule, fluoxetine group could improve the expression of PKA, BDNF, CREB in CA3and DG(p<0.05); Compared with the sham group, the expression of PKA,BDNF, CREB in hippocampal decrease in the K252a (p<0.01); Compared with the K252a group, the BSL capsule+K252a rats group appears PKA, BDNF, CREB, immune response positive products increased, the difference had no statistically significant.④Genetic testing:Compared with the control, sham group, the expression BDNF, CREB mRNA decreased in model group (p<0.01); Compared with the model group, the BSL Capsule high dose, fluoxetine group could increase the expression of BDNF, CREBmRNA (p<0.05); Compared with the sham group, the expression of BDNF, CREB mRNA decrease in the K252a rat (p<0.01); The expression of BDNF, CREB mRNA expression were significantly increased in BSL capsule+K252a, but had no difference with K252a group.Conclusion:①The BSL capsule could significantly improve the CUMS rats with depression-like behavior;②The hippocampus micro-injection of K252a could simulate CUMS induction of depression-like behavior and the pathological change;③K252a could inhibite antidepressant effect of BSL capsule, BSL have relationship with BDNF;④BSL capsule may affect model rats hippocampal neurogenesis by cAMP-CREB-BDNF signaling pathway.