Titov V N
The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552, Moscow, Russia.
Klin Lab Diagn. 2017;62(8):452-462. doi: 10.18821/0869-2084-2017-62-8-452-462.
The clearer realization is coming that in general biology, medicine, historical science, in biologic phylogenetic anamnesis of Homo sapiens a task exists only one by its significance and unresolved still: to establish historical succession of becoming of specific etiologic factors of every metabolic epidemic and to understand becoming of millions years' common pathogenesis of all metabolic pandemics. The carnivorous feeding by ocean, herbivorous feeding of ancestors of rodents and Homo sapiens by dry land; misusing carnivorous food by phylogenetically herbivorous human during last centuries, disorder of biological function of trophology, biological reaction of exotrophy, pathology of biologic functions of adaptation and endoecology, features of cognitive biological function formed etiological factors of atherosclerosis and atheromatosis. The abnormalities of biological reaction metabolism↔micro-circulation; discrepancy of mechanisms of regulation of biological reaction at 2d and 3d levels of relative biological perfection in vivo, disorder of biological function of adaptation, biological reaction of compensation formed etiological factors of metabolic arterial hypertension. The synthesis of fatty acids in phylogenesis millions of years before of glucose, preference of cells to absorb fatty acids instead of glucose; previously in phylogenesis effect of hyperglycemia, glucagon and late function of insulin formed priority of metabolism of fatty acids in energetics of organisms and glucose only in the second instance. The formation in phylogenesis of methodological mode of biological subordination in functioning of humoral mediators, incapability of insulin late in phylogenesis of blocking adaptive action of humoral mediators earlier in phylogenesis, especially in visceral fatty tissue form etiological factors of resistance to insulin. The functional limitation of cognitive biological function, difficulties in maintaining unity of internal medium of organism and effects of aphysiologic factors of external medium produces necessity of completing cognitive biological function with activation of biological reaction of apoptosis and autophagy. This occurrence forms etiologic factors of metabolic syndrome - a local pathology of early, visceral, limited in numbers of cells of pool of insulin-independent visceral fatty tissue. The inconsistency of cognitive biological function, necessity of correcting it by more effective biological function of intellect, role of insulin in energy support of new biological function - locomotion, formation of unlimited in numbers of cells а pool late in phylogenesis of insulin-dependent subcutaneous adipocytes, formed etiological factors of obesity. The biological function of depositing of fatty acids in phylogenesis in vivo is characterized by etiological dependence: depositing of fatty acids occurs in the form of non-polar triglycerides and releasing into intercellular medium occurs only in form of polar unesterified fatty acids. The features of induction with substrate, formation of positioning isoforms of fatty acids, impossibility of hydrolyzing them at effecting of hormone-dependent lipase compel to eliminate aphysiologic triglycerides from liver together with hepatocytes implementing biological reactions of apoptosis and autophagy. They become etiological factors of non-alcoholic fatty disease of liver; these are aphysiologic positioning iusoforms of triglycerides as palmitoyl-palmitol-palmitate and stearyl-stearyl-stearate. The formation of endogenous hyperuricemia in phylogenesis was initiated by 2 mutations. The first one - a gene of ascorbic acid "minus" deprived Homo sapiens of synthesis of hydrophilic acceptor of active forms of oxygen. The second one - a gene of uricase "minus" blocked synthesis of allantoin but provided a possibility of re-absorbing uric acid from a pool of primary urine and use it in vivo as an acceptor of active forms of oxygen instead of ascorbic acid under realization of biological function of endoecology,biologic reaction of inflammation.
人们越来越清楚地认识到,在普通生物学、医学、历史科学以及人类生物学系统发育记忆中,存在着一项意义重大但仍未解决的任务:确定每种代谢性流行病特定病因因素的历史演变顺序,并理解所有代谢性大流行数百万年的共同发病机制。海洋中的肉食性摄食、啮齿动物和人类祖先在陆地上的草食性摄食;在过去几个世纪中,系统发育上为草食性的人类滥用肉食性食物,营养生物学功能紊乱、外营养生物反应、适应生物学功能和内生态学病理学,认知生物学功能的特征形成了动脉粥样硬化和动脉粥样瘤的病因因素。生物反应代谢与微循环的异常;体内相对生物完善的二维和三维水平上生物反应调节机制的差异、适应生物学功能紊乱、代偿生物反应形成了代谢性动脉高血压的病因因素。在系统发育中,脂肪酸的合成比葡萄糖早数百万年,细胞优先吸收脂肪酸而非葡萄糖;在系统发育中,高血糖、胰高血糖素的作用以及胰岛素的晚期功能形成了生物体能量代谢中脂肪酸优先、葡萄糖其次的情况。体液介质功能中生物从属方法模式在系统发育中的形成,胰岛素在系统发育后期无法阻断体液介质在系统发育早期的适应性作用,尤其是在内脏脂肪组织中,形成了胰岛素抵抗的病因因素。认知生物学功能的功能限制、维持机体内部介质统一性的困难以及外部介质的非生理因素的影响,产生了通过激活凋亡和自噬生物反应来完善认知生物学功能的必要性。这种情况形成了代谢综合征的病因因素——一种早期的、内脏性的、胰岛素非依赖性内脏脂肪组织细胞数量有限的局部病理学。认知生物学功能的不一致性、通过更有效的智力生物学功能对其进行纠正的必要性、胰岛素在新生物功能——运动的能量支持中的作用;在系统发育后期形成数量无限的胰岛素依赖性皮下脂肪细胞池;形成了肥胖症的病因因素。系统发育中体内脂肪酸沉积的生物学功能具有病因依赖性:脂肪酸以非极性甘油三酯的形式沉积,只有以极性未酯化脂肪酸的形式释放到细胞间介质中。底物诱导的特征、脂肪酸定位异构体的形成、在激素依赖性脂肪酶作用下无法水解它们,迫使肝脏与实施凋亡和自噬生物反应的肝细胞一起清除非生理性甘油三酯。它们成为肝脏非酒精性脂肪性疾病的病因因素;这些是非生理性定位异构体甘油三酯,如棕榈酰 - 棕榈醇 - 棕榈酸酯和硬脂酰 - 硬脂酰 - 硬脂酸酯。系统发育中内源性高尿酸血症的形成由两个突变引发。第一个是抗坏血酸“负”基因,使人类失去了活性氧亲水性受体的合成能力。第二个是尿酸酶“负”基因,阻断了尿囊素的合成,但提供了从原尿池中重新吸收尿酸并在体内将其用作活性氧受体而非抗坏血酸的可能性,这是在实现内生态学和炎症生物反应的生物学功能时发生的。