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Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (4): 363-367.doi: 10.3736/jcim20060409

• Original Experimental Research • Previous Articles     Next Articles

Effects of blockage of hypothalamic-pituitary-adrenal cortex axis by metyrapone and Jiawei Xiaoyao Pills on immune system in mice exposed to chronic emotional stress

Yun Zhang1, Zhen-yu Wu1, Jian Xiao2, Xiao-feng Geng2, Yan-xia Guo1, Shi-jie Li3   

  1. 1. Department of Immunology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China;
    2. Department of Psychology, Peking University, Beijing 100871, China;et al.
  • Online:2006-07-31 Published:2006-07-15

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Objective

To explore the effects of Jiawei Xiaoyao Pills (JWXYP) on immune system of mice exposed to chronic emotional stress, and to compare its effects with blockage of hypothalamic-pituitary-adrenal cortex axis (HPAA) by metyrapone.

Methods

Eighty male mice were randomly divided into eight groups: normal saline-treated group, normal saline-treated stress group, JWXYP-treated group, JWXYP-treated stress group, metyrapone-treated group, metyrapone-treated stress group, metyrapone and JWXYP-treated group and metyrapone and JWXYP-treated stress group. A box of electrical shock was used to induce chronic emotional stress in mice. The metyrapone was applied to blocking the HPAA. The JWXYP, a classical formula of traditional Chinese medicine, which can alleviate the damages caused by chronic emotional stress, was also used to compare its effects with that of metyrapone. The body weight, thymus index, rate of apoptosis in thymus, serum concentration of glucocorticoid, activity of natural killer cells, lymphocyte transmission rate of mice were all measured and examined after interventions. The pathological changes of thymus tissue were observed.

Results

The thymus index, activity of natural killer cells and lymphocyte transmission rate were lower while the rate of apoptosis in thymus as well as the severity degree of pathological damages in thymus tissue were increased in the different drug-treated stress groups as compared with those in the corresponding drug-treated groups without stress. The activity of natural killer cells and the lymphocyte transmission rate induced by lipopolysaccharide were increased while the serum concentration of glucocorticoid and the severity degree of pathological damages in thymus tissue were decreased in both the metyrapone-treated stress group and JWXYP-treated stress group as compared with those in the normal saline-treated stress group. The combined intervention of metyrapone and JWXYP did not show better effects on immune system in mice exposed to chronic emotional stress than single metyrapone or JWXYP interventon.

Conclusion

Blockage of HPAA by metyrapone intervention shows a significant protective effect on immune system in mice exposed to chronic emotional stress, and the JWXYP also exerts a similar protective effect against damages induced by chronic emotional stress. The HPAA may be one of the action targets of protective effects of JWXYP.

Key words: Jiawei Xiaoyao Pills, Metyrapone, Hypothalamic-pituitary-adrenal cortex axis, Chronic emotional stress, Immune system

CLC Number: 

  • R2-03

Figure 1

Changes of body weights of mice in eight groups after interventionA: Normal saline-treated group; B: Normal saline-treated stress group; C: JWXYP-treated group; D: JWXYP-treated stress group; E: Metyrapone-treated group; F: Metyrapone-treated stress group; G: Metyrapone and JWXYP-treated group; H: Metyrapone and JWXYP-treated stress group; *P<0.05, vs normal saline-treated group; △P<0.05, △△P<0.01, vs normal saline-treated stress group."

Table 1

Thymus index and rate of apoptosis in thymus of mice in different groups（（ヌ±S, %）"

Group n Thymus index Rate of apoptosis
in thymus
Normal saline-treated
Without stress 10 0.34±0.08 17.09±5.18
Stress 10 0.27±0.06* 33.89±5.54**
JWXYP-treated
Without stress 10 0.35±0.05△ 19.12±3.69△△
Stress 10 0.29±0.09* 26.37±4.56*
Metyrapone-treated
Without stress 10 0.37±0.04△ 16.43±4.31△△
Stress 10 0.32±0.06* 23.62±6.84*
Metyrapone and JWXYP-treated
Without stress 10 0.37±0.08△ 17.42±5.26△△
Stress 10 0.31±0.07* 25.34±4.75*

Table 2

Serum concentration of glucocorticoid and activitiy of natural killer cells in spleen of mice in different groups（（ヌ±S））"

Group n Serum concentration of
glucocorticoid (μg/L)		 Activity of natural killer cells in spleen (%)
Normal saline-treated
Without stress 10 25.15±3.41 33.51±10.23
Stress 10 55.20±4.27** 20.28±11.27**
JWXYP-treated
Without stress 10 23.25±4.23△△ 36.37±11.02△
Stress 10 33.53±5.15* 22.33±10.09**▲
Metyrapone-treated
Without stress 10 21.24±2.26△△ 35.64±9.12△
Stress 10 30.78±7.14* 27.19±12.09*
Metyrapone and JWXYP-treated
Without stress 10 20.61±2.94△△ 37.21±13.74△
Stress 10 25.86±2.41* 28.16±12.20*

Table 3

Amounts of 3H-TdR incorporated in lymphocytes of mice in different groups (lymphocyte transformation rate)（ヌ±S, cpm）"

Group n Amount of 3H-TdR incorporated in lymphocytes
LPS-induced ConA-induced
Normal saline-treated
Without stress 10 13 759±419 9 421±569
Stress 10 7 154±541** 5 337±219*
JWXYP-treated
Without stress 10 13 554±520△△ 9 236±641△
Stress 10 9 881±257*△ 5 635±409*
Metyrapone-treated
Without stress 10 15 880±849△△ 9 049±831△
Stress 10 10 103±576*△ 6 915±454*
Metyrapone and JWXYP-treated
Without stress 10 15 384±999△△ 9 054±270△
Stress 10 10 323±965*△ 6 313±702*

Figure 2

Histopathological changes of thymus tissue of mice in different groups (HE staining, ×40)A: Normal saline-treated group; B: Normal saline-treated stress group; C: JWXYP-treated group; D: JWXYP-treated stress group; E: Metyrapone-treated group; F: Metyrapone-treated stress group; G: Metyrapone and JWXYP-treated group; H: Metyrapone and JWXYP-treated stress group."

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