| "Memory is the mother of wisdom". As a basic part of human thinking activities, learning memory plays a critical role in the formation of wisdom, creation of senses and accumulation of knowledge. However, when people grow middle-aged, or get tired, or become ill, their learning memory ability declines. Nowadays with the pace of daily life quickened and pressure from work increased, the issue of learning memory decline has become more and more serious and caught wide attention. It is of great practical importance to explore and figure out a set of effective treatments for the fatigue-caused memory declination.In this regard, the traditional Chinese medicine usually promote treatments based on the principle of nurturing the heart and kidney; our project, "the research of the mechanism that soothing- the- air and boosting-the-immunity medicine reduces the sport-related fatigue", which was funded by the National Natural Sciences Foundation, discovered that the mechanism of the sport-related fatigue causing memory decline was related to the decline of liver's function, and the Chinese medicines for boosting the liver had significant effect of reversing the memory decline. Then, when it comes to memory decline caused by complicated fatigue, what effects does each of these two treating methods have? To answer this question, we started with studying the traditional Chinese medicine theories and combined the lab experiments to explore the effects and the molecular biology mechanisms. We hope our findings will benefit clinical practices.1 Study of traditional Chinese medicine theoriesOur study started with literature review of the traditional Chinese medicine's understanding of memory and fatigue, focusing on the relationships between fatigue, the organs of heart, liver and kidney, and learning memory. Thus we figured out the theoretical foundations for the memory-improving methods of dredging the liver and nurturing the kidney and heart.Specifically, the heart, kidney, liver and heart-kidney interaction are closely linked to learning memory. Among them, the liver can strengthen the transportation between the heart and kidney. In view of the Five-Organ-Theory about the learning memory, the interaction of the heart and kidney with the intervention of the liver can be explained as:the heart is in charge of receiving information from the outside world, the kidney controls the information storage, and the liver is responsible for information retrieve. Because fatigue would impair the Yin Qi of the heart, the liver and the kidney, nurturing the organs according to their nature would be effective treatment. Specifically, as "the heart's desire is the gentleness", the right way to nurture the heart is to make the heart gentle; as "the kidney's desire is the strength", the right way to nurture the kidney is to make the kidney strong; as "the liver's desire is to dispense", the right way of nurturing the liver should make the liver soothed. Therefore, "supporting the heart", "enriching the kidney", and "soothing the liver", despite their different names, are all about nurturing the organs and should all be appropriate for reversing the fatigue-caused memory decline.2 Lab experimentsOur study was built on the animals' fatigue model to evaluate the changes In the animals' learning memory abilities. We also employed the lab techniques of immunohistochemistry, western blot and real time PCR, and systematically observed the fatigue models of rat's hippocampus c-fos protein expression and changes of its mRNA. We also added intervention by applying soothing liver medicine (modified SiNi), nurturing kidney and heart medicine (modified wisdom-generating soup), and combination of equal amount of the two aforementioned medicines to explore the adjustment effects of the medicines and their mechanism. The lab details and the results are as follows:2.1 The construction of the rats' fatigue modelIn this study, the animals' fatigue model was constructed by combing swimming practices with sleep deprivation, which effectively simulated the physical fatigue and mental fatigue, and therefore is a quite ideal fatigue-modeling method. Through measuring the animals'weight, observing rats under normal circumstances, during tests of balance and open spaces, and measuring the rats by the commonly used LDH Fatigue Index, this study successfully built the rats' fatigue model. The three interventions of medicine all proved to be effective.2.2 The evaluation of tired rats' learning memory ability and the effect of treating methods of soothing the liver and nurturing the heart and kidneyThis section of the study used the indexes of Y labyrinth experiment, correct reaction rate, wrong reaction counts, and the times of training needed to reach the standards, and the total reaction time to measure the changes in the animals'learning memory abilities and the adjusting effects of traditional Chinese medicine.The results indicated that there was no significant difference among the rats in learning memory ability. After the modeling, the response speed and correct rate of the rats in the model groups were significantly lower than those of the normal group. Both of the traditional Chinese medicines for soothing the live and for nurturing the heart and the kidney increased the animals'correction rate and reduced the total reaction time and the wrong reaction counts; the combination of the two medicines increased the animals'correct rate and reduced the total reaction time, the wrong reaction times, and the total time needed for training. Thus, each of the three traditional Chinese medicine treatments were effective in reversing the fatigue-caused memory decline and the combination of the two medicines proved most effective. Further this study found that the medicine for soothing the liver mainly had the effect of reducing the reaction time and the combination of the two medicines could increase the correct response rate.2.3 The immunohistochemistry studies of the effect of soothing liver and nurturing the heart and kidney on tired ratsThe results indicated that the c-fos positive reaction materials were mainly expressed by DG and CA3 in hippocampus. The rats in the models had significantly fewer IOD of DG and CA3 than the normal group. Medicine for soothing the liver and the medicine for nurturing the heart and kidney could increase the protein expression of DG and CA3; and the combined medicine could significantly increase the protein expression of DG, CA3 and CA1, and in the CA1 region, the combined medicine significantly improved c-fos protein expression.2.4 The Western blot study of the effect of soothing lever and nurturing the heart and kidney on tired ratsThe results indicated that the rats in the models had significant lower c-fos protein expression, and each of the medicine, especially the combined medicine treatment had increased c-fos protein expression.2.5 The real time PCR study of the effect of soothing lever and nurturing the heart and kidney on tired ratsThe results indicated that c-fos mRNA expression level of the model groups were significantly lower than the normal group, and the three groups received medicine treatments, to different degrees, had increases in their c-fos mRNA expression.3 ConclusionThis study, based on the literature review of previous research, explored the effects of the treatments of soothing the liver and nurturing the heart and kidney on the fatigue-caused memory decline. The theoretical study section started with traditional Chinese medicine's understanding of fatigue and learning memory to explore the relationship between fatigue and the organs of the heart, liver and kidney, and thus proved that theoretically it is appropriate to use the methods of soothing the liver and nurturing the heart and kidney to reverse the fatigue-caused memory decline. The lab section constructed animals' fatigue model with swimming practices and sleep privation, and added intervention by applying three medicine treatments (medicine of soothing the liver, medicine of nurturing the heart and kidney, and the combination of equal amount of aforementioned two medicines) on the animals. During the experiments of behavioral studies, the animals'learning memory ability significantly declined and each of the three medicine treatments had significant intervention effect to different degrees. Further, this study applied the techniques of immunohistochemistry, western blot and real time PCR and found that the monocular biology mechanism of fatigue-caused memory decline is likely to be the of hippocampal c-fos mRNA level gets reduced and then the protein expression is weakened. The applied three traditional Chinese medicines, especially the combination of medicines for soothing the liver and nurturing the heart and kidney, could significantly reverse the fatigue-caused memory decline, and the mechanism of these medicine intervention was related to the fact that the medicine for soothing the liver, the medicine for nurturing the heart and kidney, and the combined of the aforementioned two medicines could increase the c-fos expression. |
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