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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (2): 138-144.doi: 10.3736/jcim20100208

• Original Experimental Research • Previous Articles     Next Articles

Effects of Xiaotan Jieyu Recipe on behaviors of tumor-bearing rats with chronic mild stress and the mechanism

Li-juan Xiu, Pin-kang Wei,Hui-ming Lin, Bin Pang   

  1. Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • Received:2009-10-09 Accepted:2009-12-10 Online:2010-02-20 Published:2010-02-15
  • Contact: Pin-kang Wei E-mail:czzyk73@163.com

Objective

To investigate the effects of unpredictable chronic mild stress and Xiaotan Jieyu Recipe (XTJYR), a compound traditional Chinese herbal medicine, on the behaviors of Walker 256 tumor-bearing rats and to explore the mechanism.
Methods

Sixty Wistar rats were randomly divided into control group, stress group, tumor-bearing group, stress plus tumor-bearing group, fluoxetine group and XTJYR group. After treatment, sucrose solution consumption, score of ethology, body weight and serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected, expressions of Bcl-2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) proteins in hippocampus were detected by Western blotting method, and expression of Bcl-2 mRNA was measured by polymerase chain reaction method.
Results

Sucrose solution consumption, behavioral scores and body weight of rats were decreased in the stress group and the tumor-bearing group as compared with the control group. There were significant differences in expressions of Bcl-2 mRNA and Bcl-2 and p-ERK1/2 proteins in hippocampus and contents of serum TNF-α and IL-6 in the stress group and the tumor-bearing group as compared with those in the control group. XTJYR had the efficacy in improving behavioral scores of stress rats and tumor-bearing rats, down-regulating the contents of serum TNF-α and IL-6 and increasing the expressions of proteins of Bcl-2 and p-ERK1/2.
Conclusion

Tumor-bearing rats are prone to behave depressively after exposure to chronic mild stress and XTJYR can improve the behavioral scores of the rats. The mechanisms of XTJYR may relate to regulating contents of serum TNF-α and increasing the protein expressions of Bcl-2 and p-ERK1/2.

Key words: Tumor, Depression, Chronic mild stress, Drugs,Chinese herbal, Xiaotan Jieyu Decoction, Rats

Table 1

Primer sequence"

Gene Primer sequence Segment size (bp)
Bcl-2 Upper primer: 5'-GACGCGAAGTGCTATTGGT-3'
Reverse primer: 5'-CAGGCTGGAAGGAGAAGAT-3' 205
GAPDH Upper primer: 5'-TCCCTCAAGATTGTCAGCAA-3'
Reverse primer: 5'-AGATCCACAACGGATACATT-3' 308

Table 2

Sucrose solution consumption of rats in different groups before and after experiment ($\bar{x}±s$, mL/kg)"

Group n Sucrose solution consumption
Pre-experiment Post-experiment
Control 10 96.80±7.22 90.00±6.08
Tumor-bearing 10 94.00±2.92 77.80±11.48*△△
Stress 10 91.00±1.58 53.00±7.48**△△
Stress plus tumor-bearing 10 93.00±2.73 20.60±6.62**
Xiaotan Jieyu Recipe 10 92.00±5.15 66.00±6.44*△△
Fluoxetine 10 92.70±4.32 66.80±10.10*△△

Table 3

Behavioral test of rats in different groups before and after experiment ($\bar{x}±s$)"

Group n Crossing score Rearing score
Day 0 Day 28 Day 0 Day 28
Control 10 63.6±14.3 95.8±18.4 13.5±6.5 7.3±3.5
Tumor-bearing 10 57.5±24.8 53.4±22.4**△△ 9.0±3.8 5.0±3.6△△
Stress 10 68.6±17.9 45.5±14.1**△ 11.3±3.9 2.4±1.7**
Stress plus tumor-bearing 10 57.7±29.3 20.6±20.4** 10.0±4.2 1.4±1.8**
Xiaotan Jieyu Recipe 10 60.3±24.9 63.0±23.4**△△ 10.6±5.5 8.8±5.8△△
Fluoxetine 10 58.6±24.6 66.8±10.1**△△ 10.9±5.3 7.6±3.6△△

Table 4

Body weight of rats in different groups before and after experiment ($\bar{x}±s$, g)"

Group n Body weight
Pre-experiment Post-experiment Difference
Control 10 103.90±7.41 262.63±23.04 158.73±26.69
Tumor-bearing 10 109.30±5.31 209.30±9.15**△ 100.00±11.38*
Stress 10 105.40±5.38 211.40±22.74**△ 106.00±24.34*△
Stress plus tumor-bearing 10 105.40±4.77 194.70±7.86** 89.30±6.48*
Xiaotan Jieyu Recipe 10 107.20±4.62 209.70±10.11**△ 102.50±11.27*△
Fluoxetine 10 106.90±3.40 196.13±11.66** 89.23±13.08**

Table 5

Contents of serum TNF-α and IL-6 in rats in different groups after treatment ($\bar{x}±s$, ng/L)"

Group n TNF-α IL-6
Control 8 121.14±35.14 170.75±58.60
Tumor-bearing 8 181.45±20.14**△ 302.75±55.01**
Stress 8 172.17±9.92**△ 276.71±17.90*
Stress plus tumor-bearing 8 204.08±21.71** 323.00±37.95**
Xiaotan Jieyu Recipe 8 140.35±14.36*△△ 261.83±34.59*
Fluoxetine 8 149.23±19.14*△△ 251.24±65.36*

Table 6

Expressions of Bcl-2 mRNA and protein in hippocampus of rats in different groups ($\bar{x}±s$)"

Group n Bcl-2 protein Bcl-2 mRNA
Control 8 1.37±0.31 1.62±0.85
Tumor-bearing 8 1.20±0.23△△ 1.42±0.36△△
Stress 8 0.84±0.19**△ 0.63±0.29**
Stress plus tumor-bearing 8 0.54±0.26** 0.36±0.18**
Xiaotan Jieyu Recipe 8 1.59±1.02△△ 0.75±0.26**
Fluoxetine 8 1.13±0.30 1.22±0.22*△△

Figure 1

Expressions of Bcl-2 mRNA and protein in hippocampus of rats in different groupsA: Control group; B: Tumor-bearing group; C: Stress group; D: Stress plus tumor-bearing group; E: Xiaotan Jieyu Recipe group; F: Fluoxetine group."

Table 7

Expression of p-ERK1/2 protein in hippocampus of rats in different groups"

Group n p-ERK1/2 protein
Control 8 1.10±0.37
Tumor-bearing 8 0.86±0.33
Stress 8 0.62±0.43*
Stress plus tumor-bearing 8 0.52±0.45*
Xiaotan Jieyu Recipe 8 1.08±0.56
Fluoxetine 8 1.40±0.20△△

Figure 2

Expression of p-ERK1/2 protein in hippocampus of rats in different groupsA: Control group; B: Tumor-bearing group; C: Stress group; D: Stress plus tumor-bearing group; E: Xiaotan Jieyu Recipe group; F: Fluoxetine group."

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