Exploring the relationship between Ca2+and the"Qi"of TCM from the perspective of modern medicine

Ai-Wen Zhuang,Xue-Min Fan,Li-Na Ji,Xian Deng,Hong Ling,Rong-Qun Li,*

1Zhejiang Academy of Traditional Chinese Medicine,Hangzhou,310007,China.2Zhejiang Chinese Medical University,Hangzhou 310053,China.

Introduction

In the category of ancient Chinese philosophy,Qi is the extremely fine material that exists in the universe and is ubiquitous.According to the existing literature,the concept of"Qi"appeared in the pre-Qin period.The Tao Te Ching,written by Laozi(571-471 B.C.),first gave philosophical significance to the concept of"Qi".It is the original material of all things in the universe[1].On the basis of this,traditional Chinese medicine(TCM)proposes that Qi,vital and running continuously,is the most essential substance to constitute the human body and sustain its life activity.Qi is an important part of the human body,"run with sufficient Qi,run depends on Qi";at the same time,it is the driving force for inspiring and maintaining human life activities,feeling and transmitting information about various life.The Qi maintains the life process of human body,and the cessation of its movement marks the end of life.

Recognizing the essence of Qi isextremely important for the development of TCM.However,current Chinese medicine textbooks consider that Qi is the most basic substance to constitute human life activities,but does not indicate the specific material form of Qi[2].Therefore,the understanding of the essence of Qi,the Chinese medicine community has not reached a consensus,which has become a difficult problem to limit the development of TCM.In our work and study，we found that"Qi"has many similarities with Ca2+.We describe it as follows.

The source of Qi and Ca2+are similar

Qi in the body includes innate Qi,Qi of food nutrients and clear Qi of natural,which is the result of comprehensive coordination of spleen,kidney,lung and other organs.As one of the most basic 12 trace elements in human body,Ca2+is the most essentialsubstance formaintaining human life activities[2].It has similarities with the source of Qi and plays an important role in the process of Qi production.

Innate Qi

Innate Qi is the driving force of human life activities.Lingshu • Cijiezhenxie called it “genuine Qi”,and said that the combination of the congenital essence and the Gu Qi forms the genuine-Qi that nourishes the whole body.Parents give their living materials to their offspring through the form of reproductive essence,and the innate essence that the descendants receive is the foundation of the human body.The role of Ca2+in the human body also begins with fertilization,which contains Ca2+in both sperm and eggs and plays an important role in the fertilization process.After the sperm enters the egg cell,the Ca2+concentration at the sperm-egg fusion is instantaneously increased,and it is transmitted to the opposite side of the egg in the form of calcium wave,followed by a series of repeated Ca2+oscillations,causing the release of the cortical granule and blocking the multi-fertilization[3-4].At the same time,the first meiosis and the first polar body discharge were initiated.Thus,Ca2+in fertilized eggs is obtained from eggs and sperm,and both Ca2+and innate Qi come from innate.

Qi of food nutrients

The Qi of food nutrients derived from the diet.Lingshu•Yingweishenghui said that Qi in the human body comes from food.When food is taken into the stomach,its nutrients are transported to the lung.Since the lung is connected with all the channels and vessels,all the Zang Fu-organs receive Qi from the lung.TCM believes that the main physiological function of the spleen is govern transportation and transformation,and of the stomach is to receive and decompose food.The spleen transforms the diet into the nutrient part to replenish the viscera.At the same time,it provides materials for the Qi,blood,essence and liquid promotes the growth and development of the human body and maintains human life activities[5].The body gets nutrients through the diet and transforms itinto energy thatsupports body movements.Calcium in the human body comes from food,is absorbed in the form of Ca2+by the intestinal epithelium,and achieves calcium balance under the regulation of thyroxine,vitamin D3and calcitonin in the body.In the acquired source,Ca2+is obtained through diet and has the same effect as the generation of Qi of food nutrients.

Clear Qi of natural

The ClearQifrom thenaturalrelieson the respiratory function of the lungs and the receive Qi function of the kidneys to inhale the body.Su Wen•Yinyangyingxiangdalun(B.C.220~211,Han Dynasty)said that Heaven-Qi communicates with the lungs.Later generations of doctors used clear Qi of natural as oxygen,but clinical studies have found that changes in Ca2+concentration also play an Important role in respiratory regulation.Respiratory muscles are innervated by somatic motor nerves.Calcium is the triggering element of skeletal muscle excitation-contraction coupling[6].Changes in Ca2+concentration can cause contraction and relaxation of respiratory muscles such as intercostal muscles and diaphragm muscles.The resulting respiratory motion becomes the driving force for lung ventilation.Studies have also shown that,children with respiratory failure are often accompanied by hypocalcemia that is not easy to correct[7].The mechanism is that Ca2+outside the red blood cells shifts and accumulates into the cells,which reduces the cell membrane deformation and movement ability,and is easily broken by the narrow microcirculatory blood vessels,resulting in increased blood stagnation and peripheral resistance.From the above two points,although Ca2+cannot be directly obtained from nature through the lungs,itspresence has an important influence on the intake and production of clear Qi.

The function of Qi and Ca2+are unified

Qi,one of the material foundations of the human body,is the driving force for promoting human life activities,and plays a role in maintaining the life process.Nanjing said that Qi is the most basic and important element of the human body.Leijing said that people have a life,it depends on the Qi.The physiological functions of the human body are mainly promoting,warming and cooling,defending,consolidating and mediating.We found that Ca2+has similar functions to “Qi”in these respects.

Promoting

Qi is a subtle substance with strong vitality.The growth and development of the human body,the physiological activities of the viscera and meridians,the formation of the blood and body fluids,and the operation and transmission mustrely on the promotion of Qi.Correspondingly,modern medicine has found that Ca2+also has this effect on normal human life activities.

Promote growth and developmentPrimordial Qi,a driving force of human life activities,originates in the kidney and flows through the body through three-energizer.It plays a role in promoting human growth and development and reproductive function.Similarly,Ca2+has an effect on promoting osteogenesis.Ca2+is an important element that constitutes the human bones and teeth,with support and protection.At the same time,the bone acts as a calcium reservoir,which can regulate the constant concentration of extracellular fluid Ca2+to ensure the normal excitability of the tissue and directly affect the growth and development of the human body.In addition,Ca2+as an important second messenger,its changes in intracellular concentration have an effect on cell proliferation,differentiation and cell signal transmission[8-10].It can be seen that Ca2+plays a physiological role close to the primordial Qi in promoting growth and development.

Push the blood in the veinsLingshu•Jueqi(B.C.475~221,Han Dynasty)said thatZhongjiao receives Qi,absorbs the juice and changes it into red.That is what blood means.Qi deficiency will affect the formation of blood and make the body blood deficiency.Calcium plays an important role in the body.The heart's pulsation requires the combination of calcium and troponin C to cause contraction[11].Within a certain range,the concentration of Ca2+in the extracellular fluid is increased,the concentration of Ca2+in the inflow is increased,the myocardial contractility is enhanced,and the pumping function is also enhanced.Conversely,the Ca2+concentration of the extracellular fluid is reduced,the myocardial contractility is weakened,and the pumping function is also weakened,which can cause blood deficiency[12-13].TCM believes that"Qi is the commander of blood","Qi flow promoting blood transportating",Qi stagnation leads to blood stasis;when the Qi is deficient,the promotion of Qi is weakened,and it is impossible to push the blood to run in the vein,and blood stasis will occur.Studies have found that,increased intracellular Ca2+concentration in red blood cells can lead to decreased red blood cell deformability,thereby increasing blood viscosity and increasing blood flow resistance in large blood vessels[14].It can be seen that the concentration of Ca2+in red blood cells has an important effect on the erythrocyte motility,which is similar to the pathogenesis theory of blood stasis caused by Qi deficiency in TCM.

Warming and cooling

The constant body temperature,the stable of the visceral function and the orderly operation of the essence,blood and body fluids are inseparable from the warming effect of yang and the cooling effect of yin.Yibian•Qi said that Yang plays a warming role in the human body.If the yang is insufficient and the heat production is too low,there may be deficient cold lesions such as chillness feeling and fondness of warmth,limbs chilly.If the cooling effect of Yin is reduced,it can be seen that there are deficient heat lesions such as low heat and night sweats and vexing heat in chest,palms and soles.Ca2+is characterized by both Yin and Yang,and affects body temperature regulation to exert warmth and coolness.Calcium-activated potassium channels in the hypothalamus are highly temperature sensitive.Changes in temperature may cause the corresponding functional allosteric effects of the channel protein to change the excitability and discharge frequency of the neurons,and then adjust the state of the body to adapt to changes in ambient temperature[15].It can be seen that Ca2+has a functional unity with Yin and Yang,and plays an important role in the process of constantbody temperature and stable internal environment.

Defending

Qi can not only protect the body surface,but also prevent the invasion of pathogenic Qi.At the same time,it can also remove the pathogenic Qi that invade the human body[1].Suwen(B.C.220~211,Han Dynasty)said that if healthy Qi is sufficient inside the body,pathogenic Qi cannot invade the body,indicating that the Qi's defense function is normal,then the pathogenic Qi is not easy to invade;on the contrary,if the Qi's defense function is low,it can't resist pathogenic Qi.It is easy to invade the human body and cause disease,which is called:the accumulation of pathogenic Qi means the deficiency of Qi.

Ca2+plays an important role in the defense of pathogenic Qi.As a second messenger,it can transmit the stimulation signal on the cell surface to the nucleus,initiate a series of intracellular reactions,cause gene expression, cell proliferation and differentiation,thereby enhancing the phagocytic activity of immune cells.Studies on rickets have found that patients with reduced intestinal calcium absorption,resulting in low levels of Ca2+in the blood, stimulate the secretion of parathyroid hormone(PTH),elevated PTH leads to a series of reactions to increase intestinal and renal tubules to calcium absorption,maintain blood calcium stability[16].Hypocalcemia occurs when vitamin D continues to be absent and secondary hyperparathyroidism is not sufficient to maintain circulation.Therefore,the pathological mechanism may be that the decrease of blood calcium leads to the decrease of intracellular free calcium,which reduces the phagocytic activity of polymorphonuclear neutrophils(PMNs).In modern world,the study on the immunomodulatory effects of the Qi herbs Panax found that Panax polysaccharide(PPQ,the most abundant and most immunologically active substance in Panax) can increase the calcium-dependent channel opening rate,prolong the opening time and shorten the closure time,indicating that PPQ can promote lymphocyte proliferation and differentiation and IL2 production by increasing free calcium ions in activated T lymphocytes,thereby promoting cytotoxic T cell killing activity,and exerting and enhancing its immune function[17].It can be seen that Ca2+is similar to defensive Qi,and it plays a role in defending against pathogenic Qi by improving the body's immunity.

Consolidating

The consolidating effect refers to the protection,coordination and control of the liquid substances such as blood,essence and fluid in the body,preventing these substances from being lost without any reason,and ensuring that they exert normal physiological functions in the body.If the Qi failure to control blood,it will produce bleeding symptoms such as blood collapse,hematemesis,nasal discharge,and so on.

Ca2+has a similar consolidating effect like Qi,specifically showing that Ca2+is involved in platelet aggregation.Ca2+can cause platelet contraction to form a prothrombin complex,activate prothrombin to produce thrombin,thereby catalyzing the conversion of soluble fibrinogen into a network of insoluble fibrin,which exerts a hemostatic effect.If a small amount of sodium citrate is added to the blood taken out,since sodium citrate can bind to Ca2+in plasma to form calcium citrate which is not dissociated,the blood cannot be coagulated.A study found that serum calcium levels in patients with acute cerebral hemorrhage were significantly lower than normal[18].Itcan be seen thatthe change ofthe concentration of Ca2+will affect the bleeding of the patient.Ca2+may be the purpose of preventing blood clots by participating in blood coagulation,thereby reflecting the"blood-control"effect of the Qi.

Mediating

The mediating effect of the human body's Qi mainly refers to the induction of conduction information by the Qi to maintain the overall connection of the body.All kinds of life information in the human body can be sensed and transmitted through the ascending,descending,exiting and entering of Qi of the body,thus constructing a close relationship between various parts of the human body.Calcium ions also play a similar role in the two physiological processes of transmitting visceral information and expressing external stimuli.

Messenger of informationVarious information of the internalorgans can be reflected on the corresponding tissues and organs of the body surface through the load and conduction of the Qi.Such as interior-exterior relationship between kidney and bladder,Qi transformation of the bladder depends on the regulation of kidney Qi transformation.If kidney Qi is not consolidating,the bladder will not store the urine and discharge it out of body.The relationship between the kidney and the bladder is explained by the Ca2+messenger function:the kidney regulates urine metabolism by regulating the release of parathyroid hormone(P1H)and calcitonin(CT)by the detrusor to the urine of the bladder[19].A similar effect of Ca2+and Qi in transmitting visceral information was confirmed.

Expressing external stimuliQi can achieve the purpose of regulating the coordination of physiological activities of the body by sensing external information and carrying and conducting it to the organs.Stimulating information such as acupuncture,massage and other external treatment methods are carried by the induction of Qi to achieve therapeutic effects.Studies have shown that,through experiments on rabbits,the calcium concentration in the skin and superficial fascia of normal rabbits is significantly higher than that of non-acupoints,and the calcium concentration of muscle layer in Zusanli(ST36)of warm moxibustion rabbits is higher than that of non-moth moxibustion group[20].It is suggested that there may be calcium ion enrichment in the skin and superficial fascia,indicating that calcium ions may have similar functions to the“meridian Qi”. Comparing the physiological functions of Ca2+,it is also an intermediate link in the external stimulation of the excitatory body.Under normal circumstances,the concentration of Ca2+inside and outside the cell is quite different,which makes Ca2+have strong electrochemical force.When the cells are stimulated,any slight change in the permeability of the cell membrane to Ca2+will cause the cytosolic Ca2+to fluctuate significantly,resulting in a corresponding physiological effect.This is the case with calcium ion-mediated myocardial and skeletal muscle movements mentioned above.Modern research hasfound thatlowering the concentration of blood calcium ions can increase the content of excitatory transmitters in the brain and decrease the contentofinhibitory transmitters,leading to abnormal discharge of brain cells and causing seizures[21].Studies have shown that soluble polysaccharide(Atractylodes extract)may increase the expression level of adhesion-associated protein E-cadherin through polyamine and Ca2+regulation pathways to enhance intercellular adhesion-ligation[22].These all indicate that Ca2+is similar to Qi and is an intermediary substance for expression stimulation.

It can be seen that Ca2+and"Qi"have many similarities in physiological functions and are closely related.

Correlation between herbs of tonifying Qi and Ca2+

The content of calcium in Chinese medicines with Qi effectis generally higher.Some people have determined the content of trace elements in Chinese herbal medicines such as Astragalus and Glycyrrhiza.The results showed that the content of Ca and Mg in the tested herbs was the highest[23].Some people also analyzed the trace elements in Siwu decoction,Sijunzi decoction, Bazhen decoction and Shiquandabu decoction[24].The content of Ca in Sijunzi decoction is better than Siwu decoction.The content of Fe in Siwu decoction is better than that of Sijunzidecoction,and Bazhen decoction and Shiquandabu decoction,which are both tonifying Qi and blood,are rich in Ca,Fe and other elements.It seems that Siwu decoction is partial to blood,Sijunzi decoction is partial to Qi,and Bazhen decoction and Shiquandabu decoction is related to Qi and blood.In addition,according to the reference standard of TCM deficiency syndrome,some people found that the content of trace elements in the hair of patients with"Qi deficiency"was found that the content of Ca,Mn and Fe in patientswith "Qideficiency"was significantly lower than that of normal people[25].These studies further demonstrate the subtle relationship between Ca2+and Qi,providing a credible clinical basis for our findings.

Conclusions

In conclusion,there are many similarities and close relationships between Qi and Ca2+in terms of source and function.However,we cannot equate"Qi"with Ca2+unilaterally.Qi has a rich connotation.It has a more or less relationship with other substances than Ca2+.Ca2+is at least an important part of Qi in TCM.It plays a key role in regulating normal human physiology.The above were some of the our views on the relationship between"Qi"in TCM and trace element Ca2+.We hope to provide new ideas for the study of Qi essence and achieve the purpose of promoting the development of TCM.

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