Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression

doi:10.3969/j.issn.2095-4344.2014.49.001

Abstract

Abstract:

BACKGROUND: Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill has achieved good clinical efficacy, but the underlying mechanism remains unclear.

OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore antidepression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pill.

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 Pill groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pill 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 Pill groups were given oral gavage of Betel Shisanwei Ingredients Pill (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstrically administered with sodium carboxymethyl cellulose; 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 Pill plus RU486 groups were intragstrically administered with Betel Shisanwei Ingredients Pill (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 Pill. Compared with RU486 group, Betel Shisanwei Ingredients Pill administration led to changed in cortisone content, glucocorticoid receptor mRNA expression in hippocampus, hypothalamus and pituitary gland, as well as hypothalamic corticotrophin releasing hormone mRNA expression. Experimental findings indicate that, Betel Shisanwei Ingredients Pill 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 Pill is weakened.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: depression, hypothalamic-pituitary system, medicine, Mongolian traditional, feedback

CLC Number:

R318

Bao Wu-ye, Fan Ang-ran, Bai Liang-feng, Tong Hai-ying, Yu Xue, Wujisiguleng, Li Jing, Hurilebagen, Zhang Yue. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression [J]. Chinese Journal of Tissue Engineering Research, 2014, 18(49): 7873-7878.

Figures/Tables 2

2.1 实验动物数量分析所有大鼠均进入结果分析，未出现大鼠死亡或脱落现象。 2.2 槟榔十三味丸对慢性应激抑郁模型大鼠肾上腺皮质酮水平的影响由图1可见，与正常对照组相比，模型组大鼠肾上腺皮质酮水平显著升高(P < 0.05)；与模型组相比，槟榔十三味丸低、中、高剂量组大鼠肾上腺皮质酮水平均出现降低，尤其中剂量组大鼠肾上腺皮质酮水平降低尤为显著 (P < 0.05)；氟西汀对肾上腺皮质酮的高分泌也表现出一定的调节作用，RU486组由于阻断了糖皮质激素受体受体，使负反馈受到抑制，从而影响肾上腺皮质酮分泌，表现为肾上腺的皮质酮水平增加较大(与模型组相比，P < 0.01)；与槟榔十三味丸低、中剂量组相比，槟榔十三味丸低、中剂量+ RU486组大鼠肾上腺皮质酮水平升高(P < 0.01)，但其水平较RU486组降低(P < 0.01)。 2.3 槟榔十三味丸对慢性应激抑郁模型大鼠海马糖皮质激素受体mRNA表达水平的影响由图2可见，与正常对照组相比，模型组及RU486组大鼠海马糖皮质激素受体mRNA表达水平显著下降(P < 0.01)；与模型组相比，氟西汀组和槟榔十三味丸低、高剂量组大鼠海马糖皮质激素受体mRNA表达水平显著增加(P < 0.01)；槟榔十三味丸低、高剂量+RU486组与槟榔十三味丸低、高剂量给药组相比大鼠海马糖皮质激素受体mRNA表达水平显著下降(P < 0.05或P < 0.01)；槟榔十三味丸中剂量+RU486组大鼠海马糖皮质激素受体mRNA表达水平比RU486组高(P < 0.05)。 2.4 槟榔十三味丸对慢性应激抑郁模型大鼠下丘脑糖皮质激素受体mRNA表达水平的影响由图3可见，与正常对照组相比，模型组及RU486组大鼠下丘脑糖皮质激素受体mRNA表达水平显著下降(P < 0.01)；与模型组相比，氟西汀组和槟榔十三味丸中、高剂量组大鼠下丘脑糖皮质激素受体mRNA表达水平显著增多(P < 0.05或P < 0.01)；槟榔十三味丸中、高剂量+RU486组与槟榔十三味丸中、高剂量给药组相比大鼠下丘脑糖皮质激素受体mRNA表达水平显著下降(P < 0.01或P < 0.05)；槟榔十三味丸低、中剂量+RU486组大鼠海马糖皮质激素受体mRNA表达水平比RU486组增加(P < 0.05)。 2.5 槟榔十三味丸对慢性应激抑郁模型大鼠垂体糖皮质激素受体mRNA表达水平的影响由图4可见，与正常对照组相比，模型组及RU486组大鼠垂体糖皮质激素受体mRNA表达水平显著下降(P < 0.01)；与模型组相比，氟西汀组和槟榔十三味丸低、中、高剂量组大鼠垂体糖皮质激素受体mRNA表达水平显著增加(P < 0.01或P < 0.05)；槟榔十三味丸低、中剂量加RU486组与槟榔十三味丸低、中剂量给药组相比大鼠下丘脑糖皮质激素受体mRNA表达水平显著下降(P < 0.01)；槟榔十三味丸高剂量加RU486组大鼠海马糖皮质激素受体mRNA表达水平比RU486组相比上升(P < 0.01)。 2.6 槟榔十三味丸对慢性应激抑郁模型大鼠下丘脑促肾上腺皮质激素释放激素mRNA表达水平的影响由图5可见，与正常对照组相比，模型组及RU486组大鼠下丘脑促肾上腺皮质激素释放激素mRNA表达水平显著增多(P < 0.05)；与模型组相比，槟榔十三味丸低、中、高剂量组大鼠下丘脑促肾上腺皮质激素释放激素mRNA表达水平显著降低(P < 0.01)；槟榔十三味丸低剂量+RU486组与槟榔十三味丸低剂量给药组相比大鼠下丘脑促肾上腺皮质激素释放激素mRNA表达水平显著增多(P < 0.05)；槟榔十三味丸中、高剂量+RU486组大鼠下丘脑促肾上腺皮质激素释放激素mRNA表达水平比RU486组下降(P < 0.05)。"

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