[Studies of gene networks and singal transduction of kidney deficiency syndrome by syndrome differentiation through drug effects].
Three kinds of networks were summarily described in this review including the small intracellular molecular networks, the middle-scale networks of hypothalamus-pituitary-adrenal-thymus (HPAT) axis and the large network, neuroendocrine-immune (NEI) network, covering the whole organism and linking multiple systems together. The hypothesis was expressed that the "disease" or "syndrome" formed in the human body by the intervention from outside world is based on the changes of multi-molecular network. In this paper, the pattern and ability of signal transduction channel and the methods of studying changes in it were also described, and raised, herefrom, "to determine syndrome by drug effects (DSDE)" is the intervention means for studying syndrome in the light of systemic biological methods. We found Kidney-yang deficiency syndrome covered the NEI network and the regulating center located in hypothamus with Compound Bushen Recipe (CBR, Kidney-tonifying recipe). By intervention with EF, an effective component of CBR, it was found that EF can activate the immune system and the three networks, including growth axis, sex hormone axis and lymphocyte apoptosis network in HPAT axis through the downward pathway of NEI network to play its efficiency of molecular network. There are many regulation patterns of EF on networks. For example, in the network mechanism of lymphocyte apoptosis and proliferation, EF can reconstruct the balance of the opposite apoptosis related genes and proliferation related genes; EF can assemble and integrate co-stimulating molecules, transform growth factors (TGF), and several oncogenes to form an upstream factor network for initiating the proliferation and anti-apoptosis promotion; EF can simultaneously up-regulate the two opposite genes expression of IkappaB and NFkappaB in NIK/IKK/IkappaB/Rel/NFkappaB signal transduction channel, which could not only control the rising of NFkappaB in a moderate range, but also guarantee its predominant status to exert its hinge role in molecule regulating network, by which gene network regulation atlas in HPAT axis of Kidney-deficiency syndrome was observed.
Shen
Zi-yin
ZY
Institute of Intergrative Cinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040. ziyishen@21cn.com
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D003937:Diagnosis, Differential; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008516:Medicine, Chinese Traditional; D009490:Neurosecretory Systems / Q000276:immunology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D016711:Yang Deficiency / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism
D004365:Drugs, Chinese Herbal