Based On "Neuroendocrine - Endocrine - Immune Network" To Analyze The Modern Biological Basis Of "Growing Aged - Dependent"

Purpose:To explore the foundation of ‘Human’s development relies on kidney ’ and ‘kidne y corresponds to winter’ basing on biological evidence in ‘Neuro-Endocrinologic-Immuno net work’. To demonstrate the scientific rules by tracing the indicators related to‘Neuro-Endocrin ologic-Immuno network’ marking the different phases of generating-growing-prime-aging i n ages, genders, and seasonal changes in healthy population.Material and method:Literature Research:The ‘kidney stores essence’ theory literature database was used to analyze the living rules of ‘generating-growing-strengthening-aging’ and the kidney’s functioning in ruling the process physiologically and pathologically in ancient records. The modern literatures were collected to demonstrate NEI network, DNA, stem cells and the microenvironment could be taken as the biological fundamental of ‘ kidney governs generating-growing-strengthening-aging’ theory. Epidemiological investigation:Epidemiology investigation had been processed since 2011 winter to 2013 summer. Winter is defined as the 90 days from winter start day to great cold day, while Summer is defined as the 90 days from summer start day to great heat day. The cases includes 437 cases from Liaoning region, collected by liaoning university of traditional Chinese medicine, 304 cases from Shanghai region, collected by longhua hospital affiliated to Shanghai university of traditional Chinese medicine, 303 cases from Tianjin region, collected by Tianjin university of traditional Chinese medicine, which is a 1044 cases in total. All the cases were proved health by physical examination, age differing from 1 to 70. Indicators of nervous system includes Adrenaline(AD), norepinephrine(NE), dopamine(DA), acetylcholine receptor antibody(ACh), 5-hydroxy try Ptamine(5- HT), and vasoactive intestinal peptide(VIP). Indicators of endocrine system includes Growth hormone(GH), adrenocorticotropic hormone (ACTH) and cortisol(COR), estradiol(E2), testosterone(T), thyroid stimulating hormone(TSH), β-endorphin( β-EP). Indicators of immune system includes neoplasms T-lymphocyte(CD3+,CD4+,CD8+, and the ratio of CD4+ and CD8+),B lymphocyte(CD3-CD19+),NK cell(CD56+),Interleukin 1(IL 1), interleukin 2(IL- 2),interferonγ(IFNγ), and transforming growth factor(TGF-β). All the indicators detection were performed by Guangzhou King Med Diagnostics. Flow cytometry was performed to detect T-lymphocyte(CD3+,CD4+,CD8+, and the ratio of CD4+ and CD8+),B lymphocyte(CD3-CD19+),NK cell(CD56+). Chemiluminescence was performed to detect ACTH, COR,GH,E2, T; ELISA was performed to detect ACh,TSH,INFγ,IL-1,5-HT,transforming TGF-β;Immunoradio assay:AD, NE,DA,β-EP, VIP,.IL-1 Data was statistically analyzed in Scheffe, Games-Howell and t-test way by using SPSS19 software.Results:1.The changing trends of NEI network in phases of human development:Nervous system: AD levels show a W shape change overall, higher value in 1-9 years old and over 60 years old population, the lowest point is the 20 to 29 and comparing with 20-29 and 1-9 years old group, result of over 60 years old group is significantly increased(P < 0.05). DA levels show a peak at the phase of 20-29, and the lowest is over 60 years old group, which shows a significant decrease comparing with phases(P < 0.05). Ach levels show a downward trend as age goes up. The peak appears in the 1-9 years old, and dramatically declines with aging, 20-29, 30-39(P < 0.05). 5-TH shows a similar change as Ach. The result of 1-9 years old is significantly higher than other groups(P < 0.05). VIP shows rising with ages gradually, and the peak appears on the 30-39. Compared with 1-9 years of age, other all ages content increased with significantly(P < 0.05), while comparing with 30-39 group, all other groups decreases and the group of 1- 9 and 10-19 show significant difference(P < 0.05).Endocrine system: the peak of GH content appears on 10-19 age phase, significan tly higher than the other phases(P<0.05). The bottom is 40-49. ACTH data shows it’s excreted lowest at 1-9 age phases, and 10- 19, 20-29 and over 60 group all show significant higher result(P < 0.05). COR data shows it’s excreted lowest at 1-9 age phases, and all other groups show significant higher result(P < 0.05). The peak of E2 excretion is 20-29 age phase, while the bottom is at 1-9 age phase, which is signi ficantly lower than the other groups(P < 0.05). Testosterone shows the consistent res ult as E2.Immune system: The CD3+ peak appears at 1-9 years age phase, and it goes dow n as with ages(P<0.05). the peak of CD4+ excretion appears at 50-59 age phase, a nd the bottom is at 20-29 age phase(P<0.05). the peak of CD8+ excretion appears at 10-19 age phase, and the bottom is at 50-59 age phase(P<0.05). NK cells dat a shows the bottom is at 1-9 age phase and the peak appears at over 60 age phase, and significant difference between over 60 group and all the other groups(P < 0.05). IL- 2 data shows the bottom is at 1-9 age phase, significant lower than 10-19, 40-49 and 50-59 phases(P < 0.05), and the peak appears at 50-59 age phase. IFNγ data shows the bottom is at 10-19 age phase, significant lower than 30-39, 40-49, 50-59 a nd over60 phases(P < 0.05), and the peak appears at 40-49 age phase. TGF-β data s hows the peak is at 1-9 age phase, significant higher than 10-19, 20-29, 30-39, 40-49 and over60 phases(P < 0.05), and the bottom appears at 40-49.2. The changing trends of NEI network during development in genders:The difference in genders shows in the content of GH, E2, T, the change of CD4+, and CD8+. Comparing in growth hormone, women show a dramatically higher excre tion than man in all the age phases except 1-9(P<0.05). Data of Testosterone sho ws an opposite result(P<0.05). Similar changing trends in CD4+ content, while wo men have a higher content than man, significantly in 1-9, 10-19, 20-29 and 30-39 age phases(P<0.05). Similar changing trends in CD8+ content, while man have a highe r content than women, significantly in 10-19 and 30-39 age phases(P<0.05).3.changing trends of NEI network during development in seasons:There are 18 indicators of NEI network showing difference during development in seasons. NE data shows going upwards in summer and downwards in winter before 49 years old, while after 49 years old, it shows an opposite change(P < 0.05). DA d ata shows a higher excretion in summer than in winter, significantly at 1-9, 20-19, 50-59 and over 60 years old.(P < 0.05). Ach shows a higher excretion in summer than in winter, significantly 40-49 age phases(P < 0.05). VIP shows higher excretion in winter than in summer in every stages(P < 0.05). GH shows higher excretion in wint er than in summer in every stages, significantly in over 60 group(P < 0.05). ACTH shows higher excretion in winter than in summer in every stages, significantly in 30-39 and over 60 groups(P < 0.05).(P < 0.05). COR shows higher excretion in winter than in summer in every stage, significantly in20-29, 30-39, 50-59 and over 60 grou ps(P < 0.05). E2 shows higher excretion in winter than in summer in every stage, si gnificantly in30-39 age phase(P < 0.05). TSH data shows higher excretion in winter than in summer, significantly at 40-49, 50-59 and over 60 groups(P < 0.05). Β-EP data shows higher excretion in summer than winter in every age phase(P < 0.05). C D3+and CD4+ data shows higher excretion in summer than winter in every age phase(P < 0.05). CD4+/CD8+ data shows higher excretion in summer than winter in every a ge phase, significantly at 30-39 and over 60 groups(P < 0.05). B cell data shows hi gher excretion in winter than in summer in every age phase, significantly at 1-9 age phase(P < 0.05). NK cells data shows significantly higher excreted in winter than in summer in every stage(P < 0.05). IL-1 data shows higher excretion in winter than in summer, significantly at 1-9, 30-39, 40-49 and 50-59(P < 0.05). IFNγ data shows higher excretion in winter than in summer, significantly at 10-19, 30-39 and 40-49 ph ases(P < 0.05). TGF-β data shows higher excretion in winter than in summer, signif icantly at 1-9 and 10-19 age phases.(P < 0.05).Conclusion:1.‘Development relies on kidney’ emphasizes the human living process of ‘generating-gr owing-prime-aging’ is consistent with the essence stored in kidney. As the kidney esse nce gains, human grows up and gets prime, while as it declines the aging starts, whic h reflects the kidney directly dominated the growth and the living length of human bo dy. The whole process of living is related to five zang-organs and the physical feature of each phase is related to the blood-qi conditions which depends on the five zangorgans functioning. While kidney is considered as the last one in the aging order of t he five zang organs, because it is the root and basement of five zang organs’ qi and yin-yang. Lingshu·tiannian refers that exhaustion of kidney qi is the final consequen ce of five zang-ogrgans’ decline.2.‘Development relies on kidney’ theory is based on "generating" due to essence in ki dney, "growing" due to the gaining of essence in kidney, "prime" due to the exuberan ce of kidney essence, and "aging" due to essence in kidney decline.3. pathogenically, ‘Development relies on kidney’ theory shows that the deficiency of kidney essence causes disorders in embryo developing, physical development, reproduct ive function, premature aging, dementia, bone atrophy, etc.4.The biological mechanism of ‘Development relies on kidney’ is closely related to the nerve- endocrine- immune network system, especially the nerve- endocrine system. The changes of the related indicators, DA and VIP of nervous system, GH, E2, T, β-EP IL-2, B cell of endocrine system, is consistent to the changes of kidney essence i n different phases of development.5.In different phases of development, indicators of neuro-endocrine-immune network sh ows different rules. vasoactive intestinal peptide, promote renal cortical hormone, cortis ol, CD4+/CD8+ and NK cells, and interleukin 1 decreases, while beta-endorphin, CD3+、CD8+, and B cells increases.6.the difference of neuro-endocrine-immune network indicators in gender shows signific antly in sex hormones(E2, T)and GH.7.‘kidney corresponds to winter’ theory is proved by finding GH, ACTH,COR,E2, TSH, B cells, NK cells, IL- 1, IFN-γ、TGF-βconsentration increase in winter. Oppositel y, AD, DA and ACh, VIP; T β-EP in the endocrine system, CD3+、CD4+、CD4+/CD8+decreases, which explains ‘kidney tends to storing’ theory.