Effects And Functional Mechanism Research Of Kunningan On The Behavior Of Perimen-Opausal Rats Induced By CUMS

Objective:To observe the effects of Kunningan on the perimenopausal behavior of depressed rats induced by CUMS,and to explore the mechanisms of drugs.Methods:Rat age of 12-14 months, female SD rats, weighing 280-350g, randomly divided into 7 groups:normal postmenopausal control group (control group), depression model group (model group), premarin in the treatment group (Premarin group), fluoxetine in the treatment group (fluoxetine group), medicine low dose group (low dose of Chinese medicinegroup), Chinese herbal medicine dose treatment group (group treated), Chinese high-dose treatment group (Chinese high-dose group).In addition to the control group, were single-cage rearing.Support integration testing with isolated chronic unpredictable mild stress composite modeling method to Fluoxetine, Premarin masterpiece of controlled drugs, and observe the following indicators:①body weight and behavior changes;②ELISA test the Content of largerat hippocampus, hypothalamus 5-HT, NE, hypothalamic CRH, serum E2, CS;③rat hippocampus and hypothalamus morphology (HE staining):④immunohistochemistry rat hippocampus andhypothalamus BDNF, bcl-2, bax,5HTR1A,5HTR2A expression;⑤RT-PCR to detect the hippocampus, hypothalamus 5-HTR1A,5-HTR2A receptor mRNA.Results:1, the effects of Kunningan on perimenopausal rat model of depressionDepression model rats compared with control group, weight loss, sugar intake and sugar consumption were significantly lower, horizontal movement and vertical movement score decreased (P<0.05).Kunningan can reduce these changes to varying degrees, impact on body weight,in the Chinese medicine groups, the high dose group, fluoxetine group, Premarin group, the difference was not statistically significant (P> 0.05).Comparison of sugar consumption, the difference between high-dose Chinese medicinegroup,fluoxetine group and Premarin group was not statistically significant (P>0.05), but compared with the control group, the difference was statistically significant (P<0.05), Chinese medicine group treated with Premarin was no significant difference compared (P> 0.05).Comparing the percentage of sucrose preference result, Chinese high-dose group, fluoxetine group, Premarin group, the difference was not statistically significant (P> 0.05), fluoxetine group compared with the control group showed no significant difference (P>0.05).Chinese high-dose group, Premarin group and the control group was statistically significant (P<0.05).Horizontal movement in the open field test, Chinese high-dose group, fluoxetine group, compared Premarin group, the difference was not statistically significant (P> 0.05), and compared with the model group and control group the differences were statistically significant (P<0.05).Chinese medicine group compared with Premarin group has no significant difference (P> 0.05).In the vertical movement, Chinese high-dose group, fluoxetine group, compared Premarin group, the difference was not statistically significant (P> 0.05), compared with the control group, the difference was statistically significant (P<0.05).2 The effects of Kunningan perimenopausal depression on endocrine hormones in ratsModel group compared with the control group of hypothalamic CRH, serum CS levels increased (P<0.05); Kunningan can reduce the level of hypothalamic CRH,medicine in high dose group compared the fluoxetine group and Premarin group the difference was not statistically significant (P> 0.05), but compared with the control group, the difference was statistically significant (P<0.05). high dose group inChinese medicine compared Premarin group, the difference was not statistically significant (P> 0.05).Kunningan can reduce serum level,the mid-does Chinese medicine group and medicine in high dose group compared the fluoxetine group and Premarin group, the difference was not statistically significant (P> 0.05), but compared with the control group, the difference wassignificance (P<0.05).Model of serum E2 level was decreased than the control group (P<0.05), Kunningan can increase the level of E2,Chinese low-does group,Chinese mid-does group and medium dose groups and fluoxetine group compared with the model group showed no significant difference on E2 levels (P> 0.05).Chinese high-dose group compared the fluoxetine group, Premarin group, the control group and the model group,the difference was significantly (P<0.05).3 The effects of Kunningan on perimenopausal depression model of the hippocampus, hypothalamus 5-HT, NE content The content of Hippocampus and hypothalamus 5-HT, NE in the rats of depression model group was declined(P<0.05), Kunningan can improve the content of 5-HT in the hippocampus of the depression model group, in the hippocampus the difference between Chinese medicine, the high dose group and Premarin groupcomparison was not statistically significant (P> 0.05), and the fluoxetine group, compared with the control group, the difference was statistically significant (P<0.05).In hypothalamus, Chinese high-dose group, fluoxetine group, Premarin group, compared with the control group, the difference was not statistically significant (P> 0.05).Kunningan can improve the content of NE in the hippocampus, high dose of Chinese medicine, Premarin group, compared with fluoxetine group, the difference was not statistically significant (P> 0.05), but compared with the control group, the difference statistically significant (P<0.05).In hypothalamus, Chinese high-dose group, Premarin group, compared with fluoxetine group, the difference was not statistically significant (P> 0.05), which Premarin compared with the control group showed no significant difference (P>0.05), Chinese high-dose group, fluoxetine group compared with the control group significantly (P<0.05).4 The effects of the Kunningan on perimenopausal depression model of the hippocampus, hypothalamus morphologyNeurons in Depression in hippocampus and hypothalamic of rats has changed glial cells increased infiltration of inflammatory cells.In Treatment groups the Pathological changes of hippocampus, hypothalamus were improved than that in model group, fluoxetine group, Premarin group and Chinese medicine group were better than the other.5 The effects of Kunningan on the expression of perimenopausal depression model group's BDNF in hippocampus, hypothalamus.The expression of hippocampus, hypothalamus BDNF in depression model rats decreased (P<0.05), Kunningan increase the hippocampus and hypothalamus of BDNF expression, Chinese high-dose group compared with the fluoxetine group showed no significant difference (P> 0.05), but with Premarin group, compared with the control group significantly (P<0.05). 6 The effects of Kunningan on the expression of hippocampal Bcl-2, Bax in perimenopausal depression model ratsThe expression of rats Bcl-2, Bax-positive cell in depression model group was incresed, Bcl-2/Bax values decreased significantly compared with the control group (P<0.05), Kunningan can increase Bcl-2/Bax ratio, in the hippocampus, Chinese high-dose group compared with the fluoxetine group, Premarin group and the control group, the difference was not statistically significant (P> 0.05).In hypothalamus, Chinese high-dose group compared with the Premarin group and fluoxetine group showed no significant difference (P> 0.05), with model group and the control group significantly (P<0.05).7 The effects of Kunningan on the expression of hippocampus, hypothalamus 5HTR1A,5HTR2A in perimenopausal depression model groupThe expression of 5HTR1A positive cells in depression model rats' hippocampus and hypothalamus compared with the control group of positive cells decreased (P<0.05).Kunningan increase 5HTR1A expression, in the hippocampus,the difference between Chinese high-dose group, fluoxetine group and Premarin was no significant difference (P> 0.05). In hypothalamus area, the difference between Chinese high-dose group,fluoxetine group and Premarin was no significant difference (P> 0.05), Chinese medicine low-does and mid-dose group compared with Premarin was no significant difference (P> 0.05).The expression of 5HTR2A positive cells in depression model rats' hippocampus compared with the control group of positive cells increased (P<0.05) Kunningan can reduce the expression of 5HTR2A.Chinese high-dose group compared with fluoxetine group and Premarin has no significant difference (P> 0.05).The expression of 5HTR2A positive cells in Hypothalamic area between all the groups showed no statistically significant difference (P> 0.05).8 The effects of Kunningan on the subtype receptor mRNA of the hippocampus, hypothalamus 5-HTR1A,5-HTR2A in perimenopausal depression modelIn depression model rats,the expression capability of hippocampus, hypothalamus of 5-HTR1A subtypr receptor mRNA cmpared that in the control group decreased (P<0.05); Kunningan can improved the expression capability of receptor subtypes in rat 5-HTR1A mRNA.In the hippocampus, Chinese high-dose group was stronger than Premarin groups and fluoxetine group (P<0.05), in hypothalamus, the Premarin and fluoxetine group compared with Chinese mid-does medicine group showed no significant difference (P> 0.05), but compared with the high dose group significantly (P<0.05), Chinese high-dose group compared with the control group showed no significant difference (P> 0.05).The expression level of rats hippocampus, hypothalamus 5-HTR2A subtype receptor mRNA in the depression model compared with the control group increased (P <0.05),Kunningan can declined 5-HTR2A receptor mRNA expression, in the hippocampus, the high dose group in Chinese medicine werestronger than Premarin group and the fluoxetine group (P<0.05).In hypothalamus, Chinese high-dose group compared with the control group showed no significant difference (P> 0.05),with the fluoxetine group and Premarin significantly (P<0.05), The low-does and the mid-does group in Chinese medicine were weaker than that in the fluoxetine group, Premarin group (P<0.05).Conclusion:Perimenopausal Kunningan can improve the behavior of rat model of depression, its mechanism may be adjusted the expression of Neuroendocrine hormones and the content of hippocampus and hypothalamus monoamine neurotransmitters, BDNF, Bcl-2, Bax,5HTR1A,5HTR2A.