ABSTRACT
OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group， model group， fluoxetine group （positive control of western medicine， 4.17 mg/kg）， Xiaoyao powder group （positive control of TCM， 1.88 g/kg） and Wenyang jieyu decoction low-dose， medium-dose and high-dose groups （1.25， 2.50， 5.00 g/kg）， with 15 rats in each group. Except for blank group， the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model， meanwhile the mice were given relevant medicine intragastrically， once a day， for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected， and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected， the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected， and the number of dendritic spines was determined. RESULTS Compared with blank group， model group suffered from the symptoms such as hair loss， fear of cold， curling up； sucrose preference rate， indexes of adrenal gland， thymus gland and spleen，serum levels of cyclic adenosine phosphate （cAMP）， brain-derived neurotrophic factor and gamma-aminobutyric acid， the ratio of cAMP to cyclic guanosine monophosphate， the contents of norepinephrine， dopamine and 5-hydroxy-tryptamine， the expressions of PI3K， Akt， mammalian target of rapamycin， and the number of dendritic spines in the hippocampus were significantly decreased （P＜0.01）. The time of immobility， level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased （P＜0.01）. Compared with model group， depression symptoms of rats in each administration group were improved， and the above indexes were mostly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang， regulate the secretion of neurotransmitters， and activate PI3K/Akt signaling pathway， thus playing a role in protecting hippocampal neurons.
ABSTRACT
ObjectiveTo observe the effect of Wenyang Jieyu decoction （WYJY） on the hippocampal structure of depressed rats with kidney-yang deficiency. MethodThe 105 SD rats were randomly divided into normal group， model group， fluoxetine group （4.17 mg·kg-1）， Xiaoyaosan group （1.88 g·kg-1）， and low-， medium- and high-dose （1.25，2.50，5.00 g·kg-1） WYJY groups，15 in each group. The depression model was induced by subcutaneous injection of corticosterone in rats except for those in the normal group and the rats were orally administered once a day for 28 days. The depression-like behaviors of rats were observed by sucrose preference test， novelty-suppressed feeding test， forced swimming test， and open field test. The morphology of hippocampal neurons was observed by hematoxylin-eosin（HE） staining， and the density of hippocampal neurons was detected by Nissl staining. The ultrastructure of hippocampal synapses was observed by transmission electron microscopy （TEM）. The expression of synaptophysin （SYP）， postsynaptic density-95 （PSD95）， and apoptosis-related protein Caspase-3 in hippocampal neurons was observed by immunohistochemistry， and bromodeoxyuridine （BrdU） and doublecortin （DCX） were used to observe the apoptosis and regeneration of hippocampal neurons. ResultWYJY could improve weight loss in depressed rats. As revealed by the behavioral tests， the model group showed depression-like behaviors， which were relieved in the WYJY groups and the positive drug groups. HE staining showed that the nuclei of hippocampal neurons in the model group were constricted， deeply stained， and sparsely arranged， while the neurons in the WYJY groups and the positive drug groups were significantly improved. Nissl staining demonstrated that the cell density of the model group was lower than that of the normal group （P<0.05）. Compared with model group， the groups with drug intervention showed increased cell density （P<0.05） and compact arrangement. According to the results in TEM， compared with normal group， the model group showed shortened synaptic active zone （P<0.05）， widened synaptic cleft （P<0.05）， and thinned tight zone （P<0.05）. Compared with model group， the groups with drug intervention showed shortened synaptic active zone （P<0.05）， narrowed synaptic cleft （P<0.05）， and thickened tight zone （P<0.05）. As displayed by the results of immunocytochemistry and immunofluorescence， compared with the normal group， the model group showed decreased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and increased protein expression of Caspase-3 （P<0.05）. Compared with the model group， the groups with drug intervention showed increased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and decreased protein expression of Caspase-3 （P<0.05）. ConclusionWYJY can promote the regeneration of hippocampal neurons in rats and improve the depression of rats.