Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression / 中国组织工程研究

ABSTRACT

BACKGROUND:Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil has achieved good clinical efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore anti-depression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pil. METHODS: Eighty male Wistar rats were randomly divided into ten groups according to the sugar consumption test (with eight rats in each group) normal control group, model group, fluoxetine group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups. Except normal control group, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rising, to establish depression models. In the meantime, rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups were given oral gavage of Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstricaly administered with sodium carboxymethyl celulose; rats of RU486 group were given abdominal subcutaneous injection of RU486 from day 21 after modeling; rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups were intragstricaly administered with Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) and subcutaneous injection of RU486 from day 21. RESULTS AND CONCLUSION:Compared with normal control group, cortisone content increased significantly (P < 0.05), the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland decreased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression increased significantly in the model group and RU486 group. Compared with model group, cortisone content decreased, the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland increased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression decreased significantly in rats treated with Betel Shisanwei Ingredients Pil. Compared with RU486 group, Betel Shisanwei Ingredients Pil administration led to changed in cortisone content, glucocorticoid receptor mRNA expression in hippocampus, hypothalamus and pituitary gland, as wel as hypothalamic corticotrophin releasing hormone mRNA expression. Experimental findings indicate that, Betel Shisanwei Ingredients Pil can directly regulate excessive secretion of glucocorticoid, and improve the dysfunction of hypothalamic-pituitary-adrenal axis central negative feedback through increasing glucocorticoid receptor mRNA expression and decreasing corticotropin releasing hormone mRNA expression. After the hypothalamic-pituitary-adrenal axis negative feedback pathway is blocked, the effect of Betel Shisanwei Ingredients Pil is weakened.