| Object:The purpose of this study is to discuss on the influence of Xiaotan jieyu prescription on cancer related depression and discuss the effect of unpredictable chronic mild stress and Xiaotan-Jieyu prescription upon the behavior of Walker 256 tumor-bearing rats and its mechanism.Methods: In clinical study, cancer related depression patients were divided into Chinese medicine group and control group, were assessed by SDS and HAMD scores for four weeks. The effect was valued by score-reducing rate of HAMD.In experimental study, rats were divided into stress, tumor, S-T, ST-XTJY, ST-FLX, control group, observing the effect of chronic unpredicatable mild stress (CUMS) on the sucrose consumption, activity and body weight, so establishing the stressed tumor-brearing rat model. The levels of serum TNF-α, IL-6, hippocampal function and on the mRNA and protein levels of Bcl-2, ERK1/2 and CREB in their hippocampus were observed also.Results:1,Before treatment, no difference was found between Chinese medicine group and control group all P>0.05. The SDS and HAMD scores of Chinese medicine group were significantly lower than that before treatment, all P<0.05. Efficacy evaluation showed that effective rate of Chinese medicine group was 90.63%(29/32), and that of control group was 47.82%(11/23)(P<0.05).2,Before test, no difference was found between sucrose consumption, behavioral scores, and body weight, P>0.05. 28 days of CUMS can reduce the sucrose consumption, behavioral scores, body weight gain and serum Albumin and A/G of tumor-bearing rats. The stressed tumor-bearing rats had less body weight gain, lower behavioral scores and lower serum Albuminthan stressed non-tumor-bearing rats, all P<0.05. The tumor volume of S-T group was bigger than stress group 2 weeks later. But no difference was found between thus two group 3 weeks or 4 weeks later.3,After the exposure to CUMS for 4 weeks, the sucrose consumption, behavioral activities scores of rats in both ST-XTJY group and in ST-FLX group were higher than those of rats in S-T group, all P<0.05, and no difference was shown between ST-XTJY and ST-FLX. Great differences were shown both in body weight gain and serum Albumin between ST-XTJY and S-T groups, while no difference was shown between ST-FLX and S-T group. Xiaotan-Jieyu prescription can alleviate the CUMS-induced changes caused by CUMS.4,The level of serum TNF-αand IL-6 of S-T, Stress and Tumor groups were all higher than those in control group. The level of serum TNF-αin S-T group was higher than that in ST-XTJY and ST-FLX groups (P<0.05), while no difference was shown in serum IL-6 in the other three groups. The levels of serum TNF-αand IL-6 of ST-XTJY and ST-FLX were lower than that in S-T group, all P<0.05, and there was no difference between ST-XTJY and ST-Fluoxetine.5,A marked decrease in mRNA and protein levels of Bcl-2, p-ERK1/2 and p-CREB were found in the hippocampus of rats in stress group and S-T group compared with those in control group. The mRNA level of Bcl-2 in hippocampus in S-T group decreased more than that in stress group. The administration of Xiaotan-Jieyu prescription resulted in a significant increase in protein levels of Bcl-2, p-ERK1/2 and p-CREB. No difference was shown between ST-FLX and ST-XTJY in the levels of Bcl-2 protein and p-ERK1/2 in hippocampus of rats, but a difference in p-CREB proterin between them.6,The correlation analysis showed that p-CREB was correlated with serum TNF-αnegatively(r=-0.401,P=0.023), but correlated with Bcl-2 protein and mRNA and p-ERK1/2 in hippocampus positively (r=0.613,P=0.000;r=0.486,P=0.005;r=0.488,P=0.006).Conclusion:1,Xiaotan Jieyu prescription(Bailong jieyu particle) can treat cancer related depression effectively. That proved that the sputum-qi interplay is the mechanism of cancer related depression.2,CUMS can reduce the average sucrose consumption, behavioral scores, body weight gain and serum albumin, which indicated that tumor-bearing rats were prone to behave more depressively than non-tumor-bearing rats after being exposed to CUMS. Tumor, by increasing the inflammatory reaction, can be taken as a stressor, playing an important role in the pathogenesis of cancer related depression.3,A negative correlation was found between the expression of p-CREB in hippocampus proper and levels of serum TNF-α, while a positive correlation between the expression of p-CREB and Bcl-2 protein, mRNA and p-ERK1/2. The p-CREB protein maybe a target of treatment for cancer related depression. 4,Those changes caused by CUMS were relieved in stressed tumor-bearing rats administered with Xiaotan-Jieyu prescription. It can decrease serum TNF-αand IL-6 and increase p-CREB, p-ERK1/2 and Bcl-2 protein, which helps protect neurons and maintain the normal function of hippocampus.
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