| Being the core of theoretical system of traditional Chinese medicine (TCM), the theory of correspondence between time and zang-organ shows the innate thought pattern of TCM. The holism of correspondence between man and nature permeated all medical theories of TCM, including physiology, pathology, diagnostics, therapeutics, health cultivation and so on, guiding us to realize vital movement of human body. Therefore it is extremely important to research the theory of"the kidney dominating bones"or the essence of zang-fu manifestation from the angle of correspondence between time and zang-organ. Currently, using traditional method and modern science and technology to find out the regular pattern that how TCM realizes human body and explaining its scientific connotation in modern language have became a chief aim in the research of basic theory of TCM.1. ObjectiveStarting from the concept of global regulation in the theory of correspondence between time and zang-organ, integrating the traditional thought pattern into the design and research of experiment, this study planned to use"time"to survey the connotation of"zang-organ"from the perspective of physiological function of"the kidney dominating bones". We tried to reveal the essence of"the kidney dominating bones"by the method of cell signal transduction so as to provide a new direction and target for TCM theoretical research as well as for clinical disease prevention and treatment.2. Method2.1 Theoretical researchUtilizing the three levels of methodology, which are the level of philosophy, general methodology and specific methodology and by means of the explanation and analysis of the connotation of"the kidney dominating bones"and investigative evidence, we proposed the standpoint that"the kidney dominating bones"was the embodiment of global regulation and adaptable regulation in accordance with season and discussed the starting point of the experimental research.2.2 Clinical research2.2.1Thought pattern of the designAs the units of systematical functions, the zang-fu organs are the integrated meanings in anatomy, physiology and pathology. Broadly speaking, kidney regulates hypophysis-pituitary-thyroid axis while in a narrow sense anatomic kidney functions in the"the kidney dominating bones". The kidney is an important organ participating in the bone metabolism. Although with the advance of blood purification technology uremia patients'survival rate and life quality have been obviously improved, attack rate and perniciousness of renal osteodystrophy are increasing. Starting from the theory of correspondence between time and zang-organ, this study aimed at researching the connotation of"the kidney dominating bones"and finding the connection between renal osteodystrophy and season by comparing the changes of renal function and biochemical indicator in winter and summer. It would provide some new ideas for the prevention and treatment in accordance with seasons.2.2.2 General dataAccording to the diagnostic criteria of modern medicine and TCM as well as inclusion and exclusion criteria, 39 cases of chronic renal failure patients were selected from Xi Yuan hospital affiliated to China Academy of Chinese Medicine Science in 2006.2.2.3 ItemsGeneral data includes name, gender, age, onset time, the time of the first hemodialysis, diagnosing of modern medicine and TCM, the time of the latest hemodialysis. Investigation items contain renal function indicator, biochemical indicator, blood routine examination, etc. Clinical data was taken within 7 days before or after summer solstice and winter solstice.2.2.4 Statistical methodSPSS12.0 (using T test, ANOVA test) for analysis2.3 Experimental study2.3.1 DesignThe study researched thyroid axes and photosensitive superior position adjuster pineal gland, choosing the important messengers of transmembrane signal switching such as cAMP,cGMP and IP3 as objects and observing seasonal morphological changes of thyroid as well as seasonal changes of bone metabolism under physiological state.2.3.2 Experimental animalSprague-Dawley male rats, ranging from 180 to 200 grams in weight, were randomly divided into the control group, the model group (ligation of arrow vein and removal of pineal gland) and the false operation group (ligation of arrow vein and without removal of pineal gland). The rats lived in natural light and under room temperature (17±20C in winter and 25±20C in summer), ate and drank freely. Pineal gland removal and false operation were carried out one month before the winter solstice and summer solstice. And then those rats were killed in the winter solstice or summer solstice2.3.3 Test methodsRadio-immunity for IP3 and BGP assaying, enzyme linked immunosorbent assay for cAMP,cGMP and BALP assaying, light microscope for observing morphology of thyroid.2.3.4 Statistical methodSPSS12.0 (using T test, ANOVA test) for analysis 3. Results 3.1 Result of theoretical study 3.1.1 Based on the holism, the concept of correspondence between time and zang-organ determine that when realizing the vital movement, TCM focus on entirety, unity and connection. This traditional methodology coincides with modern medical model, called physiology-psychology-society-circumstance model.3.1.2 As two main factors of the theory of correspondence between time and zang-organ, time and zang-organ are dialectically related."Time"affects functions of"zang-organ"while the latter receives information from the former and also is characterized by some spatio-temporal features. So this concept is the core of TCM theory.3.1.3 Using the theory of correspondence between time and zang-organ to find out the mechanism of global regulation and adaptable regulation in accordance with time. The principles of entirety, orderliness, interconnection and dynamic state are all the characteristics of global regulation of kidney in TCM.3.1.4 It was found from the research that kidney and bone were closely related to each other because of the homology in embryogenesis and relativity in molecular biology. Anatomic kidney, functional kidney regulating bone metabolism by hypothyroid axes and adaptable regulation in accordance with season proved the connotation of TCM kidney system as a functional unit.3.1.5 The working hypothesis based on the relativity between the"the kidney dominating bones"and cell signal transduction was as follows: the former was the embodiment of global regulation and adaptable regulation in accordance with time; being an inducing factor, less illumination time in winter would active the second messenger to transmit messages, initiating the changes of internal organs in morphology and function, which then generates physiological effect of"the kidney corresponding to winter"3.2 Results of the clinic research3.2.1 Effect of winter and summer on the functions of renal osteodystrophy CREA and BUN values in winter and summer were significantly higher than those of the control group, showing seasonal change; there was a significant difference between summer and winter for BUN (P< 0.05).3.2.2 Effect of the winter and the summer on the parathyroid hormone of renal osteopathy PTH value in winter and summer was of no statistical significance (P>0.05), but it was significantly high in winter and low in summer.3.2.3 Effect of winter and summer on the blood routine test of renal osteopathy WBC, RBC and HB values in winter and summer were of no statistical significance (P>0.05), but HB value was evidently lower than the normal.3.2.4 Effect of winter and summer on the biochemical indicator of renal osteopathy. There was a significant difference between summer and winter for CL but the values of other indicators were of no statistical significance, but the content had an increasing tendency compared with the normal.3.3 Results of experiments3.3.1 Effect of winter and summer on IP3 in cell signal transductionThe control group: the value of IP3 of hypothalamus was lower in winter than in summer (P<0.01); while that of thyroid gland was significantly lower in winter than in summer (P<0.01).The model group: The seasonal difference of hypothalamus and thyroid gland between summer and winter disappeared.3.3.2 Effect of winter and summer on cAMP and cGMP in cell signal transduction cAMP:The control group: the content of cAMP in the hypothalamus showed significantly lower in winter and higher in summer (P<0.01); the value of cAMP of the false operation group showed significantly lower in winter and higher in summer (P<0.01).The content of cAMP in the pituitary gland showed lower in winter and in higher in summer (P<0.05); the content of cAMP of the false operation group showed significantly lower in winter and higher in summer (P<0.01).The content of cAMP of the thyroid gland showed significantly lower in winter and higher in summer (P<0.01); the content cAMP of false operation showed significantly lower in the winter and in the higher summer(P<0.01).The model group: the normal difference of hypothalamus and pituitary gland between summer and winter disappeared. There was significant difference for the content of thyroid gland between summer and winter for cAMP (P< 0.01).cGMP:The control group: the content of cGMP in the hypothalamus showed significantly lower in the winter and higher in summer (P<0.01); the content of cGMP of the false operation group showed significantly lower in winter and higher in summer (P<0.01). The content of cGMP in pituitary gland showed lower in winter and higher in summer (P<0.05).The content of cGMP in thyroid gland showed significantly lower in winter and higher in summer(P<0.01); the content of cGMP of the false operation group showed significantly lower in winter and higher in summer(P<0.01).The model group: there was a difference for the content of the model group in the hypothalamus between summer and winter for cGMP (P< 0.01), and there was a difference for the value of the model group of the false operation group in pituitary gland between summer and winter for cGMP (P< 0.05); the normal difference of thyroid gland between summer and winter disappeared. cAMP/cGMP:The control group: the content of cAMP and cGMP in the hypothalamus, pituitary gland , thyroid gland showed higher in cAMP lower in cGMP, there was no significant difference for the content of cAMP/cGMP in the hypothalamus, pituitary gland , thyroid gland(P>0.05), but the content of cAMP/cGMP in the thyroid gland showed the trend of lower in winter and higher in summer.The model group: it was shown that the normal difference of cAMP/cGMP in pituitary gland between summer and winter disappeared(P>0.05).3.3.3 Effects of winter and summer on serum bone metabolismThe content of CICP in the serum showed significantly higher in winter and lower in summer; the content of BALP showed significantly statistical significance (P<0.01), it showed significantly higher in winter and lower in the summer; the content BGP of the simulation in winter and summer showed no significantly statistical significance (P>0.05). It was shown that the normal difference of CICP, BALP and BGP between summer and winter disappeared(P>0.05). There was no significant difference for the content of CICP, BALP and BGP(P>0.05)between simulative winter and summer(P>0.05), but the content of BALP and CICP higher in winter and lower in the summer.3.3.4 Effects of winter and summer on thyroid gland in morphologyIn the control group, winter and summer influenced the thyroid gland in morphology differently, but in the operation group the influence was slight.3.3.5 The rough model for the mechanism of"the kidney dominating bones"Via the path of optomeninx-suprachiasmatic nucleus-pineal gland, the decreased illumination makes pineal gland secrete more melatonin in winter. MT directly acts on thyroid axis to start the second messenger system through G-protein-coupled receptors on cell envelope, adjust the metabolic activity of IP3 by means of repressing the physiologic reaction of cAMP so as to regulate the physiological effect of cells. Morphological Changes of thyroid tissue increase its hormone secretion, which then raise the contents of BALP and CICP and enhance the metabolism of osteoblast. At the same time, T3 can adjust the activity of osteoclast and finally strengthen the metabolism of bones. The evidence manifest bones reserve substance to adapt to winter, and prepare for growth in spring and summer.4. ConclusionsThis study investigated the changes of thyroid axis in winter from the perspective of cell signal transduction; and the results indicated the seasonal changes of the second messenger in hypothalamus, pituitary and thyroid were due to seasonal changes in winter and summer, which made thyroid gland change in morphology and then the bone metabolism; it was coincident with the idea that"the kidney dominating bones and storage and also corresponding to winter"and further illustrated that five zang-organs not only existed in anatomy but also are systematical functional units. Viewed from the perspective of"season", the essence of zang-organs is determined by the characteristics of correspondence between man and nature such as global regulation and adaptable regulation in accordance with season.Based on the holistic regulation, this study was in line with the holism and the characteristics of zang-fu manifestation, and used the integrated thinking model to study the essence of"the kidney dominating bones"; it included theoretical, clinical and experimental study and combined with signal transduction theory. So it provided the guidance to the study of basic theory of TCM, especially to the zang-fu manifestation theory. With the pathological observation on renal osteodystrophy in winter and summer and seasonal changes of renal function in patients, this study also provided some instructional suggestions of climate concerned prevention and therapy. |
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