The Study On How Stress Affects The Liver Fuction And The Underlying Mechanisms

Stress is one of the major risk factors which accounts for the increased incidence of a number of common life-threatening disorders. It is now getting highlight in that stress not only produces some nervous system depended mental problems, but also results in some substantial structure change beyond the nervous system like the heart, the liver etc,causes the functional impirement of these organs. But little is known on the question whether impairment to non-nervous organs was in parallel with or consequent to that of brain. Meanwhile, although the importance of stress in life appears to be significant, the cellular and molecular mechanisms involved in the pathophysiology of stress remains largely unknown especially for those non-neuronal organs. The case for liver is even worse than that for the cardiovascular system which received strong focus and developed in a relatively fast speed. Only recently has scientific evidence been obtained to demonstrate how stress exacerbates liver diseases. There still lack study on how stress affects the function of normal liver and what are the underlying mechanisms. Objective:This study aims to illuminate the relationship between the stress induced liver function impairment and that of brain and to detect the molecular change of liver under a most commonly used stress model, immobilization.Method:In the current study, the typical antidepressant paroxetine (20 mg/kg) or Chinese prescription Sinisan (100 mg/kg) which is proved to protect the liver were used during the 14 repeated daily RSs (RS, 6 h/d). The body weight was measured under different treatments. The enzyme activities of serum glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP) as well as Morris Water Maze (MWM) were used to evaluate the liver function or spatial learning and memory, respectively. In the other study,we employed BDNF, KDR and Bax as the candidate molecules which are suggested to be involved in the liver response to immobilization stress. To test the different effect of acute and repeated immobilization, we evaluated the mRNA level for BDNF, KDR and Bax in liver tissue after the rats received one acute immobilization or 15 repeated daily immobilization stresses.Result:The 14 RSs caused significant decrease of growing speed as revealed with the body weight (P < 0.05, vs vehicle), while pretreatment with paroxetine or Sinisan kept the stressed rats grow at the normal speed (P > 0.05, vs vehicle). The 14 RSs caused significant increase of sera enzyme acitivities for GPT and ALP (P < 0.05, vs vehicle), as well as significant decrease of spatial learning and memory abilities (P < 0.05, vs vehicle). Fourteen daily paroxetine treatments increased the abilities for spatial learning and memory but had no effect on the elevated enzyme activities. On the other hand, fourteen daily Sinisan treatments did not affect RS impaired spatial learning and memory abilities while reversed the RS induced increase of enzyme activities. In the other study, acute immobilization stress significantly (P < 0.01, vs control) increased the mRNA level for KDR (114.8% of control) but not for BDNF mRNA. While, fifteen repeated immobilization stresses significantly (P < 0.01, vs control) decreased the mRNA level for BDNF (82.22% of control) but not for KDR. Surprisingly, neither acute nor repeated immobilization changed the expression level of Bax.Conclusion:Restraint stress induced impairment of liver function is in parallel with the impairment to brain. Repeated RSs can impair the brain or liver function via different mechanisms. KDR or BDNF is involved in the liver response to acute or repeated immobilization, respectively. Locally synthesized Bax is not strongly involved in the liver response to acute or repeated immobilization stress.