CN101172140A - Nutritive composition for accelerating hemopoietic stem cell proliferation and hemoglobin synthesis - Google Patents
Nutritive composition for accelerating hemopoietic stem cell proliferation and hemoglobin synthesis Download PDFInfo
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Abstract
The invention discloses a nutritional composition for promoting the proliferation of hematopoietic stem cells and the synthesis of haemoglobin. The invention is characterized in that the invention comprises raw materials and the proportion by weight as follows: 90 to 110 nucleotide, 20 to 30 parts of arginine, 20 to 30 parts of lysine, 10 to 20 parts of cysteine, 25 to 35 parts of glycin, 20 to 30 parts of histidine, 110 to 130 parts of lecithin, 50 to 70 parts of cephalin, 0.4 to 0.6 parts of vitamin E, 5 to 7 vitamin C, 0.02 to 0.04 parts of folacin, 0.05 to 0.07 parts of vitamin B2, 0.07 to 0.08 vitamin B6, 0.0001 to 0.0002 parts of vitamin B12, 0.5 to 1.5 parts of ferrum, 0.5 to 0.7 parts of zinc, 0.4 to 0.6 parts of manganese, 14 to 16 parts of boxthorn amylase, and 14 to 16 parts of grapestone aqueous extract. The invention can evidently improve the quantity of hemoglobins (Hb), red blood cells (RBC), white blood cells (WBC) and blood platelets (Plt) in the blood, can stimulate the proliferation of the marrow hematopoietic stem cells to lead the hematopoietic stem cells to be evidently increased, can evidently improve the number of mitochondrion in the cell and have obvious recovery function to the damage of liver and spleen.
Description
Technical field:
The present invention relates to a kind of medicines and health protection alimentation composition, especially a kind ofly can obviously promote hemopoietic stem cell proliferation and the synthetic alimentation composition of hemoglobin.
Background technology:
According to The World Health Organization (WHO) investigation, the whole world has 3,000,000,000 people that anemia is in various degree arranged approximately, and wherein male's sickness rate is about 10%, and the women is greater than 20%.Over surplus in the of nearly 10 year, China comprises that the various exsanguine sickness rate of nutritional anemia is high, and modern city and towns resident's anemia incidence rate every year is with 10%～15% speed increment.
Except that nutritional anemia, according to the cause of disease and pathogeny, anemia also can be divided into because of erythropoiesis reduce and because of hematoclasis too much or the anemia two big classes due to losing.
Because the anemia due to erythropoiesis reduces mainly contains: hemopoietic stem cell proliferation and dysdifferentiation, CFU-E or precursor proliferation and differentiation obstacle, DNA dyssynthesis (megaloblastic anemia), hemoglobin dyssynthesis (hypochrosis) and number of mechanisms or agnogenic anemia etc.
Since hematoclasis too much or the anemia due to losing mainly contain: erythrocyte internal abnormality (film defective, azymia, globin shortage etc.), erythrocyte outside unusual (physics, chemistry, infection, antibody-mediated, mononuclear phagocyte superfunction, hypersplenism and lose blood etc.).
At present, have for the Therapeutic Method of anemia following several, equal problems of various degrees.
1. edible function food.The domestic existing kind more than 20 of functional food of improving nutritional anemia, leading enrich blood product such as Donga Colla Corii Asini, XUEER, heart K, woman's edge, mend snow, beneficial blood and give birth to etc., main component has two classes: the one, and chemosynthesis compositions such as ferrous lactate, ferrous porphyrin, ferrous sulfate, lemon ferrous phosphate, vitamin C; Another kind of is animals and plants and medicinal herb componentses such as Colla Corii Asini, Mel, Gallus Domesticus, Fructus Lycii, soybean phospholipid, salad oil, Radix Ginseng, Radix Angelicae Sinensis, the Radix Astragali, Cera Flava.But because the auxotype anemia is except the iron deficiency factor, also with to lack multiple reasons such as folic acid, vitamin relevant, so prior function food is unsatisfactory to the health-care effect of anemia, can only be as accesary foods, and it is very high to cut out the probability of back recurrence.
2. take hematopoietic stem cell transplantation (HSCT), exist donor deficiency and rejection two hang-ups.
3. employing gene therapy exists and waits to solve the key issue that improves transfection efficiency.
4. external source is carried EPO (erythropoietin) or androgen, exists the problem that side effect is difficult to avoid.
Summary of the invention:
The present invention is in order to solve existing in prior technology the problems referred to above, provide a kind of taking convenience, recurrence probability low, be free from side effects, do not produce rejection, can obviously promote hemopoietic stem cell proliferation and the synthetic alimentation composition of hemoglobin.
Technical solution of the present invention is: a kind of promotion hemopoietic stem cell proliferation and the synthetic alimentation composition of hemoglobin is characterized in that raw material and weight ratio are as follows: nucleotide 90～110, arginase 12 0～30, lysine 20～30, cysteine 10～20, glycine 25～35, histidine 20～30, lecithin 110～130, cephalin 50～70, vitamin E 0.4～0.6, vitamin C 5～7, folic acid 0.02～0.04, vitamin B
20.05～0.07, vitamin B
60.07～0.08, vitamin B
120.0001～0.0002, ferrum 0.5～1.5, zinc 0.5～0.7, manganese 0.4～0.6, lycium barbarum polysaccharide 14～16, Semen Vitis viniferae extract 14～16.
Best-of-breed technology solution of the present invention is that raw material and weight ratio are as follows: nucleotide 100, arginase 12 5, lysine 25, cysteine 15, glycine 30, histidine 25, lecithin 120, cephalin 60, vitamin E 0.5, vitamin C 6, folic acid 0.03, vitamin B
20.06, vitamin B
60.06, vitamin B
120.0001, ferrum 1, zinc 0.6, manganese 0.5, lycium barbarum polysaccharide 15, Semen Vitis viniferae extract 15.
The present invention carries out 19 kinds of nutritional labelings such as nucleotide reasonably combined, and cooperatively interacting acts on human body, can obviously improve blood hemoglobin (Hb), erythrocyte (RBC), leukocyte (WBC) and platelet (Plt) quantity; Can stimulate the propagation of marrow hemopoietic stem cells, make the hematopoietic stem cell showed increased; Obviously improve intracellular plastochondria number; Damage to liver, spleen has tangible restitution, is applicable to malnutritional anemia (iron deficiency anemia and folic acid and vitamin B
12Malnutritional anemia), anemia and hematoclasis anemia too much or due to losing due to erythropoiesis reduces.
Description of drawings:
Fig. 1 is normal control group mice peripheral blood film * 1000.
Fig. 2 is aplastic anemia model group mice peripheral blood film * 1000.
Fig. 3 is normal control group mouse bone marrow cells smear * 1000.
Fig. 4 is aplastic anemia model group mouse bone marrow cells smear * 1000.
Fig. 5 is normal control group mouse bone marrow cells transmission electron microscope picture * 8000.
Fig. 6 is aplastic anemia model group mouse bone marrow cells transmission electron microscope picture * 8000.
Fig. 7 is normal control group mouse marrow stem cell clone form figure.
Fig. 8 is aplastic anemia model group mouse marrow stem cell clone form figure.
Fig. 9 is normal control group mouse liver pathological section * 400.
Figure 10 is aplastic anemia model group mouse liver pathological section * 400.
Figure 11 is normal control group mouse spleen pathological section * 400.
Figure 12 is aplastic anemia model group mouse spleen pathological section * 400.
Figure 13 is embodiment of the invention high dose group mouse bone marrow cells smear * 1000.
Figure 14 is dosage group mouse bone marrow cells smear * 1000 in the embodiment of the invention.
Figure 15 is embodiment of the invention low dose group mouse bone marrow cells smear * 1000.
Figure 16 is that the embodiment of the invention influences sketch map to the mouse bone marrow cells hematopoietic stem cell.
Figure 17 is embodiment of the invention high dose group mouse marrow stem cell clone form figure.
Figure 18 is dosage group mouse marrow stem cell clone form figure in the embodiment of the invention.
Figure 19 is embodiment of the invention low dose group mouse marrow stem cell clone form figure.
Figure 20 is the influence sketch map of the embodiment of the invention to the mouse marrow stem cell clone.
Figure 21 is embodiment of the invention high dose group mouse bone marrow cells transmission electron microscope picture * 8000.
Figure 22 is that the embodiment of the invention is to the mitochondrial sketch map that influences of aplastic anemia mice.
Figure 23 is embodiment of the invention high dose group mouse bone marrow cells hepatic pathology section * 400.
Figure 24 is dosage group mouse bone marrow cells hepatic pathology section * 400 in the embodiment of the invention.
Figure 25 is embodiment of the invention low dose group mouse bone marrow cells hepatic pathology section * 400.
Figure 26 is embodiment of the invention high dose group mouse bone marrow cells spleen pathological section * 400.
Figure 27 is dosage group mouse bone marrow cells spleen pathological section * 400 in the embodiment of the invention.
Figure 28 is embodiment of the invention low dose group mouse bone marrow cells spleen pathological section * 400.
The specific embodiment:
Embodiment 1:
With nucleotide (base class or ucleosides or mononucleotide, oligonucleotides or polynucleotide, mixed nucleotides or ribonucleic acid or DNA (deoxyribonucleic acid) etc.), arginine, lysine, cysteine, glycine, histidine, lecithin, cephalin, vitamin E, vitamin C, folic acid, vitamin B
2, vitamin B
6, vitamin B
12, ferrum, zinc, manganese, lycium barbarum polysaccharide, Semen Vitis viniferae extract (oligomeric anthocyanagen-GSPE has another name called procyanidin) is raw material, by weight proportioning, can make tablet, powder, oral liquid, capsule etc. according to a conventional method.The raw material consumption should guarantee that the effective ingredient weight ratio is as follows: nucleotide 90～110, arginase 12 0～30, lysine 20～30, cysteine 10～20, glycine 25～35, histidine 20～30, lecithin 110～130, cephalin 50～70, vitamin E 0.4～0.6 (a-TE), vitamin C 5～7, folic acid 0.02～0.04, vitamin B according to calculating such as effective ingredient concentration
20.05～0.07, vitamin B
60.07～0.08, vitamin B
120.0001～0.0002, ferrum 0.5～1.5, zinc 0.5～0.7, manganese 0.4～0.6, lycium barbarum polysaccharide 14～16, Semen Vitis viniferae extract 14～16.Can choose raw material in above-mentioned scope according to patient age, body weight etc. and arrange in pairs or groups, consumption per day is a benchmark with nucleotide 900～1100mg usually.
Embodiment 1 raw material model and source are as table 1.
Table 1
| Sequence number | Material name | Model | Manufacturer |
| 1 | Nucleotide | Food stage 98% content | The Fujian ZHENAO HESUAN |
| 2 | Arginine | Cp2005 | The flourish aminoacid company limited in Ji, Jinzhou |
| 3 | Lysine | Cp2005 | The flourish aminoacid company limited in Ji, Jinzhou |
| 4 | Cysteine | Cp2005 | The flourish aminoacid company limited in Ji, Jinzhou |
| 5 | Glycine | Cp2005 | The flourish aminoacid company limited in Ji, Jinzhou |
| 6 | Histidine | Cp2005 | The flourish aminoacid company limited in Ji, Jinzhou |
| 7 | Lecithin | U.S. USP23 | U.S. ADM company (Beijing phoenix gift essence is asked trading agent) |
| 8 | Cephalin | Food stage 6437 | U.S. ADM company (Beijing wind gift essence is asked trading agent) |
| 9 | Vitamin E | Cp2005 | Johnson ﹠ Johnson's life nutriment company limited is thought in the Xinchang |
| 10 | Vitamin C | Cp2005 | Dongbei Pharmaceutical General Factory |
| 11 | Folic acid | U.S. USP23 | Zhenjiang high roc pharmaceutcal corporation, Ltd |
| 12 | Vitamin B 2 | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 13 | Vitamin B 6 | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 14 | Vitamin B 12 | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 15 | Ferrum | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 16 | Zinc | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 17 | Manganese | Cp2005 | Zhengzhou Ruipu Bioengineering Co., Ltd. |
| 18 | Lycium barbarum polysaccharide | 15% lycium barbarum polysaccharide | Xuancheng, Anhui BAICAO plant industry and trade company limited |
| 19 | Semen Vitis viniferae extract | Xuancheng, Anhui BAICAO plant industry and trade company limited |
Embodiment 2:
Other are with embodiment 1, the raw material consumption should guarantee that final contained components by weight is as follows: nucleotide 100, arginase 12 5, lysine 25, cysteine 15, glycine 30, histidine 25, lecithin 120, cephalin 60, vitamin E 0.5, vitamin C 6, folic acid 0.03, vitamin B according to calculating such as concentration
20.06, vitamin B
60.06, vitamin B
120.0001, ferrum 1, zinc 0.6, manganese 0.5, lycium barbarum polysaccharide 15, Semen Vitis viniferae extract 15.60 kilograms of old people's consumptions of body weight are benchmark with nucleotide 1000mg.
Pharmacological action:
1. create basic condition for marrow hemopoietic stem cells propagation
(1) replenishes ucleotides nutrition (base class or ucleosides or mononucleotide, oligonucleotides or polynucleotide, mixed nucleotides class or ribonucleic acid class or DNA (deoxyribonucleic acid) etc.) and not only help the duplicating of gene, the autonomous reparation of lesioned gene, gene expression, also help mitochondrial propagation, this just is the synthesizing and improve bone marrow microenvironment of the propagation of hematopoietic stem cell, haemachrome and hemoglobin, and basic condition has been created in the metabolism of promotion liver,spleen,kidney and system genitale metabolism and hemopoietic regulatory factor.
(2) provide arginine, lysine and cysteine, for the chromosomal formation of chromosome, spermatogonium and spermatid (dna replication dna) of hematopoietic stem cell creates conditions.
Arginine, lysine are the chromosomal main alkaline histone of hematopoietic stem cell, spermatogonium, and arginine, cysteine are the proteic main histone of sperm nucleus, therefore help the gene replication of hematopoietic stem cell, the growth promoter of sperm; And spermine, spermidine that smart (bird) propylhomoserin forms are again cell growth promoters, and this not only helps hemopoietic stem cell proliferation, also helps the cellular metabolism of corresponding organ.
(3) provide folic acid, vitamin B
12, zinc, manganese and lecithin, cephalin to be to promote erythropoiesis.
Folic acid and vitamin B
12: the synthetic of DNA needs deoxythymidine acid, and deoxythymidine acid needs N
5, N
10-methylene tetrahydrofolate, the latter transforms generation by tetrahydrofolic acid under the catalysis of methylferase.Vitamin B
12Be the coenzyme composition of methylferase, therefore, lack folic acid or vitamin B
12, deoxythymidine acid is generated reduce, influence the synthetic and erythrocytic propagation of DNA then.
Zinc: the generation of cell is divided into two parts, the size of cell and the quantity of cell.The former depends on proteinic synthetic, and the latter relates to the synthetic of DNA.Many zinc enzymes participate in these two synthetic, zinc deficiency can make that the quality and quantity of histone changes in the chromatin, influences duplicating and breaking up of cell.
Manganese: generate manganese superoxide dismutase (MnSOD), the protective wire plastochondria is to satisfy the energy requirement of hematopoietic stem cell.
Lecithin, cephalin: be mitochondrion and hematopoietic stem cell, mature erythrocyte membrane component.
2. promote the synthetic of hemoglobin
Promote the propagation of hematopoietic stem cell, be the synthetic prerequisite of having created of hemoglobin, provide corresponding nutrition again to promote the synthetic of hemoglobin.
(1) promote haemachrome synthetic
Glycine and ferrum: be the base stock of haemachrome, and the synthetic glycinamide synthetase participation of glycine participation purine nucleotides is synthetic, helps hemopoietic stem cell proliferation again.Ferrum and protoporphyrin are combined into haemachrome, and haemachrome combines with globin and forms hemoglobin; The release of body self-energy is relevant with the quantity that the intracellular plastochondria is built up ferrum, and the heart, liver, kidney etc. have in the organ of height physiological activity ability and biochemical function, and the ferrum of accumulating in the cell mitochondrial is many especially.
Vitamin C: make ferrous maintenance reducing condition be beneficial to absorption, make folic acid change tetrahydrofolic acid and N into
5-formyl tetrahydrofolic acid, and lysine, cysteine, histidine, folic acid, vitamin B
2, B
12And the hypoxanthine in the nucleic acid metabolism process etc., all can promote ferrous absorption and utilization.
Vitamin B
2, B
6: vitamin B
2Lack, can cause hypoplastic bone marrow and anemia; Vitamin B
6Be the coenzyme of haeme synthetase, it is synthetic to reduce haemachrome during shortage.
Manganese: generate manganese superoxide dismutase (MnSOD), mainly be present in the mitochondrion, to eliminate free radical, the protective wire plastochondria is the synthetic creation basic condition of haemachrome.
(2) promote the synthetic of hemoglobin
Histidine: the important component of globin.
Vitamin E: by regulating the biosynthesis that pyrimidine bases participate in DNA, the synthetic cofactor of ubiquinone synthesizes relevant with hemoglobin.
3, promote spleen, kidney and liver metabolism
Spleen: nucleotide is provided, helps the homergy of spleen; And the arginine that provides, lysine promote the metabolic while of spleen cell help the synthetic phagocyte of spleen strengthen plain, to strengthen the secretion of macrophage to old and feeble and impaired erythrocytic phagocytosis and EPO.
Kidney: studies have shown that, all be absorbed in supplemented with exogenous RNA, the DNA4h, be distributed as in the macromolecule DNA body: liver 5%, spleen 4%, kidney 3%; The corresponding nutrition of the embodiment of the invention will help the secretion of the homergy and the EPO of kidney; And provide arginine to alleviate the synthetic burden of kidney.
Liver: nucleotide nutrient that provides and related substances thereof have alleviated the burden of liver de novo synthesis nucleic acid again when helping the liver homergy.90% EPO is produced by kidney, and institute is surplus then mainly to be produced by Kupffer cell in the liver, and the synthetic main position of haemachrome is bone marrow and liver.Liver not only has scavenging action to the distortion erythrocyte, and most albumin, Fibrinogen in the blood plasma, and the α-globulin of part, β-globulin are synthetic by liver.
4, promote reproduction metabolism and short androgen synthetic
It is that spermatogonium propagation has been created condition with meiosis that nucleotide, arginine, lysine are provided; And the propagation of replenishing to mature sperm of cysteine provides assurance; Provide histidine then for to have created condition to the proteic conversion of the sperm nucleus that is rich in arginine, cysteine by spermatocyte histone-arginine, lysine.Androgen mainly comes from testis, adrenal gland and ovary, and the replenishing of nucleotide, arginine, lysine is homergys of these secretion bodies of gland condition that provides the foundation.
Lecithin: it is synthetic to participate in adrenal gland's parahormone.
Vitamin E: form relevant with fertility with sperm.
Vitamin C: generate relevant with adrenocortical hormone.
Ferrum: iron deficiency influences Cellular respiration, and then influences sperm function.
Zinc: basonuclin is a kind of zinc finger-like albumen, regulates the formation of the sperm centriole of formation phase, mitochondrion rearrangement and acrosome; The concentration of plasma testosterone and dihydrotestosterone can raise.
Lycium barbarum polysaccharide: sexual function is had certain restitution.
Androgenic increase, short kidney EPO increases and stimulates hematin synthetic, stimulates bone marrow to promote erythropoiesis.
5, promote thymus and T lymphocyte regulating action to hemopoietic
Nucleotide: thymus index (organ weights and weight ratio) is significantly improved, and the lymphocyte of propagation needs nucleotide, it is the formation that quick-fried formula forms unit that T lymphocyte and product thereof can promote red, regulates erythropoiesis jointly with EPO.
6, improve oxidation resistance to improve the hemopoietic environment
(1) vitimin supplement E, vitamin C
Vitamin E: main fat-soluble antioxidant, can remove superoxide anion and singlet oxygen, stop lipid peroxidation, with the effect of the collaborative performance of selenium glutathion peroxidase.
Vitamin C: remove oxygen-derived free radicals,, prevent lipid peroxidation with the vitamin E coupling.
(2) provide cysteine, vitamin B
2, ferrum, zinc and nucleotide to be to improve the anti-oxidative defense ability of microbody in the cell
Cysteine: one of glutathion component is big with the vitamin E synergistic effect.
Vitamin B2: participate in the oxidized form of glutathione reduction.
Ferrum: participate in forming catalase, peroxidase, reduce lipid peroxidation.
Zinc: participate in synthetic superoxide dismutase, eliminate free radical.
Manganese: synthetic manganese superoxide dismutase, eliminate free radical.
Nucleotide: its metabolite uric acid is a kind of very strong free radical scavenger, and it is in the antioxidation contribution of blood plasma: the albumen sulfydryl is 50%, uric acid 25%, vitamin C 15%, a-tocopherol 5%.Additional nucleotide not only helps the synthetic of gene expression, microbody generation and multiple antioxidase, and the RNA that produces in the nucleic acid metabolism process, guanine, xanthine, hypoxanthine and uracil etc., and its oxidation resistance all is higher than vitamin E.
Lycium barbarum polysaccharide: improve SOD content.
Semen Vitis viniferae extract: eliminate free radical.
The enhancing of oxidation resistance can reduce the attack of free radical, improves the hemopoietic condition of bone marrow and bone marrow microenvironment.
7, improve genetic autonomous ability of regulation and control
(1) homergy of promotion nucleic acid in vivo
Nucleotide: be the member that provides the foundation of DNA, RNA metabolism in the body.
Arginine: promote carbamyl phosphate from the synthetic pyrimidine nucleotide of pyrimidine.
Glycine: participate in synthetic glycinamide synthetase and participate in the de novo synthesis of purine nucleotides.
Histidine: generate one carbon unit and participate in the de novo synthesis of nucleic acid.
Vitamin E: by regulating the biosynthesis that pyrimidine bases participate in DNA.
Vitamin C: the main biochemical reaction that participates in forming in the nucleus DNA.
Folic acid: its derivant tetrahydrofolic acid is the carrier of one carbon unit.
Vitamin B
6: generating a carb gene, is purine, pyrimidine synthesis material.
Vitamin B
12: as lacking, then folic acid sinks into methopterin formation, causes DNA to synthesize essential N
5, N
10Macrocytic anemia etc. takes place in-methylene folic acid deficiency.
Ferrum: can promote β-carotene to change into vitamin A and participate in purine metabolism, iron deficiency, DNA is synthetic to be reduced.
(2) the autonomous reparation for gene replication and lesioned gene creates conditions
Promote to remedy nucleic acid metabolism synthetic and de novo synthesis, provide precondition for gene replication and reparation.
It is that the dna replication dna (chromatin formation) of somatic cell, spermatogonium and sperm has been created material base that arginine, lysine and cysteine are provided.
Zinc: the RNA polymerase component, zinc deficiency, then the activity of archaeal dna polymerase reduces.Zinc also is that RNA and DNA and ribosome are stablized necessary material.
The vitamin E that provides, vitamin C are the chemical renovation agent of DNA damage; And nucleic acid metabolism product-uric acid, the still renovation agent of the DNA base of oxidated damage.
Lycium barbarum polysaccharide: the repair ability that improves DNA.
(3) mitochondrion propagation provides energy foundation for gene from master regulation
The mitochondrion propagation that copies as of the homergy of nucleic acid and gene has been created primary condition; Arginine is the encoding proteins and the receptor protein of mitochondrion password, and lysine is the mitochondrion receptor protein; Lecithin and cephalin then are the main lipid composition of mitochondrial membrane; Vitamin B
6And vitamin B
12Relate to lipid metabolism, and vitamin B
2Then promote mitochondrial energy metabolism with ferrum and manganese.Mitochondrion propagation is laid a good foundation for hemopoietic stem cell proliferation and the synthetic of haemachrome again when providing energy for body.
Experimental data:
One. the foundation of Induced Aplastic Anemia Mice model
BALB/c mouse adopts subcutaneous injection acetylphenylhydrazine 100mg/kg, after X ray 2.0Gy irradiation next day, in the 5th day cyclophosphamide 80mg/kg lumbar injection of test, repeats above step on the 15th day but do not give ray to handle.With simple equivalent normal saline corresponding site injection is the normal control group.The result shows:
1. compare with the normal control group, fur appearred in aplastic anemia model group mice successively from 7 days lax fluffy and disorderly, and glossiness reduces, and the part mice has depilation and skin lesion.Simultaneously mice becomes thin, spirit fades in not goodly, and the color of the lip eyelid is pale, movable to be reduced, few food, weight loss.
2. compare with the normal control group, all significantly reductions of erythrocyte (RBC), leukocyte (WBC), hemoglobin (Hb) and platelet (Plt) in the aplastic anemia model group mice peripheral blood (
*P＜0.01) (sees Table 2, Fig. 1, Fig. 2).
The comparison of the 45th day normal control group of table 1 modeling and aplastic anemia model group mice peripheral hemogram
| Group | n | Hb(g/L) | RBC(×10 12/L) | WBC(×10 9/L) | Plt(×10 9/L) |
| Normal control group aplastic anemia model group | 18 22 | 162.72±16.48 76.27±19.92 * | 9.99±1.31 3.47±1.42 * | 9.69±2.03 2.27±0.59 * | 860.83±290.35 333.36±271.55 * |
The t check is compared with matched group
*P＜0.01
3. bone marrow smear shows, compares with the normal control group, and oil droplet appears in aplastic anemia model group mice part bone marrow smear, and the comprehensive depletion of bone marrow is the hypertrophy obstacle, and hematopoietic cell reduces, and non-hematopoietic cell increases; The mature erythrocyte size is consistent, does not have obvious olistherozone; Megalokaryocyte lack as, thrombocytopenia is dispersed in distribution (seeing Fig. 3, Fig. 4); The bone marrow transmission electron microscope shows that the normal matched group of mitochondria number obviously reduces (seeing Fig. 5, Fig. 6) in the aplastic anemia model group mouse hematopoietic stem cell.Unclear or the disappearance of ridge, endoplasmic reticulum and nuclear mould have expansion in various degree; Soft-agar cloning forms experiment and shows, aplastic anemia model group clone number be starkly lower than normal group (
*P＜0.01, Fig. 7, Fig. 8).
4. the pathological section of liver, spleen shows, the liver organization edema is obvious, and it is clear that leaflet structure is owed, and most of hepatocyte kytoplasm is loose, light dying, and occurs the cavity that differs in size in the endochylema, karyopyknosis, thickening of nuclear membrane, chromatin engrain.Hepatic sinusoid and central vein expansion, congested companion hemorrhage (seeing Fig. 9, Figure 10); Spleen is enlargement slightly, and the acini lienalis number reduces, and germinal center is not obvious, and the spleen organizational structure is loose, and snius lienis expansion, hyperemia are the anemia shape, visible splenic arterioles wall thickening in subregion and vitreous degeneration (seeing Figure 11, Figure 12).
In sum, the Induced Aplastic Anemia Mice model that the method that adopts acetylphenylhydrazine, X ray, cyclophosphamide combined to use makes up, every index is evaluated after testing, meets the aplastic anemia model.Observed through 45 days, pathological changes continues to exist, and is similar to people's aplastic anemia performance, and the modeling process operation is simple, the length of holding time.The method not only improves the survival rate of aplastic anemia mice, and helps the broad research of subsequent experimental.
Two. the facilitation of 2 pairs of Induced Aplastic Anemia Mice of the embodiment of the invention
On the basis of setting up the aplastic anemia mouse model, adopt the embodiment of the invention 2 research that experimentizes, the result is as follows:
1. experiment is divided into groups and flow process
According to the drug dose of animal pharmacology and the design analysis of Comprehensive Experiment, be divided into: 1. normal control group; 2. aplastic anemia model group; 3. high dose group, with 1445.55mg/kg.d to mouse stomach; 4. middle dosage group, promptly with 963.7mg/kg.d to mouse stomach; 5. low dose group, with 674.59mg/kg.d to mouse stomach.
Each group is all handled by the method afford test of aplastic anemia modelling except that the normal control group, carry out treating in the 7th day in test, high, medium and low dosage group is irritated stomach with corresponding dosage to the mice of aplastic anemia modelling respectively, once a day, finishes (the 45th day) until experiment.Each experimental group in modeling the 11st, 30,45 days, is randomly drawed mice respectively, and detection experimentizes.
2. result
2.1 influence to aplastic anemia mice peripheral blood
By table 2 as seen, the alimentation composition group of various dose and aplastic anemia model group compare, all significantly risings of its peripheral hemoglobin and blood (Hb), erythrocyte (RBC), leukocyte (WBC) and platelet (Plt) (
*P＜0.01); Erythropoietin (Epo) since compensation content reduce (
*P＜0.01); And be dose-effect relationship.Illustrate that alimentation composition has facilitation (seeing Table 3) to the Induced Aplastic Anemia Mice peripheral blood.
Table 2 alimentation composition is to the influence of aplastic anemia mice peripheral blood
| Group | n | Epo | Hb(g/L) | RBC(×10 12/L) | WBC(×10 9/L) | Plt(×10 9/L) |
| Dosage group low dose group in the matched group model group high dose group | 18 22 18 18 18 | 48.27±12.49 1054.64±152.85 202.30±69.76 * 357.06±72.65 * 598.97±132.06 * | 162.72±16.48 76.27±19.92 152.53±32.67 * 131.13±17.98 * 121.13±14.12 * | 9.99±1.31 3.47±1.42 9.43±2.64 * 7.07±1.24 * 6.16±1.28 * | 9.69±2.03 2.27±0.59 7.31±2.29 * 4.07±0.65 * 3.24±0.31 | 860.83±290.35 333.36±271.55 823.67±394.74 * 778.67±190.80 * 602.73±147.99 * |
The t check is compared with model group
*P＜0.01
2.2 influence to aplastic anemia mouse bone marrow cells hematopoietic stem cell
Bone marrow smear shows that the alimentation composition group of various dose and aplastic anemia model group compare, the hematopoietic cell showed increased (see Fig. 3,4,13,14,15,16,
*P＜0.01); Soft-agar cloning forms experiment and shows, medication group clone number apparently higher than the aplastic anemia model group (Fig. 5,6,17,18,19,20,
*P＜0.01).Show that alimentation composition can stimulate the propagation of aplastic anemia mouse bone marrow cells hematopoietic stem cell, promote aplastic anemia mouse marrow stem cell clone's formation, the effect of being significantly improved of aplastic anemia mouse bone marrow cells inhibitory state.
2.3 to the mitochondrial influence of aplastic anemia mouse bone marrow cells hematopoietic cell
Under the bone marrow transmission electron microscope, select the identical class cell of form to carry out the mitochondrion counting, the result shows that the alimentation composition group of various dose and aplastic anemia model group compare, this class intracellular plastochondria number showed increased (see Fig. 7,8,21,22,
*P＜0.01).Show that alimentation composition can promote the mitochondrial increase of aplastic anemia mouse bone marrow cells hematopoietic cell.
2.3. influence to aplastic anemia Mouse Liver, spleen
The pathological section of liver, spleen shows that the alimentation composition group of various dose and aplastic anemia model group compare, the liver organization decrease in edema, and leaflet structure is obviously clear, and the hepatocyte form is normal; Spleen recovers normally gradually, but still has part hyperemia (seeing Fig. 9,10,23,24,25, Figure 11,12,26,27,28).Show that alimentation composition has remarkable restitution to Induced Aplastic Anemia Mice liver, spleen.
Three, conclusion
1. the embodiment of the invention all has remarkable facilitation to Induced Aplastic Anemia Mice peripheral hemoglobin and blood (Hb), erythrocyte (RBC), leukocyte (WBC) and platelet (Plt).
2. the embodiment of the invention can significantly promote the propagation of aplastic anemia mouse bone marrow cells hematopoietic stem cell, thereby to the damage effect of being significantly improved of mouse bone marrow cells.
3. the embodiment of the invention can significantly promote the mitochondrial increase of aplastic anemia mouse bone marrow cells hematopoietic cell.
4. the embodiment of the invention has obvious restitution to the damage of Induced Aplastic Anemia Mice liver, spleen.
List of references:
(1) Liu Zhiwei is write " blood nourishing function food ", Chemical Industry Press, in March, 2005 front page, the 4th, 6,7,9,10,11,32～34 page.
(2) Zhang Zhinan chief editor " the erythrocyte disorder basis is with clinical ", Science Press, in October, 2000 front page, the 56th page.
(3) work such as Du Bing " progress of hematopoietic stem cell ", Chuanbei Medical College's journal, the 18th the 4th phase of volume of December in 2003, the 190th page.
(4) Feng Xianwei chief editor " the medical science philosophy of technology ", the People's Health Publisher, in October, 2002 front page, the 57th page.
(5) Zhou Airu chief editor " biochemistry ", the People's Health Publisher, in January, 2004 sixth version, the 192nd page.
(6) Yu Shouyang chief editor " progress of Chinese health food ", People's Health Publisher, January calendar year 2001, the 481st page.
(7) Chen Yuan chief editor " free radical basic medical and Pathophysiology " People's Health Publisher, in October, 2002 front page, the 149th page.
(8) work such as Ri Songyong political affairs department, Liao Meizhu translates " anticancer food nucleic acid ", the Taiwan youth publishing house, in July, 1997 first edition, the 135th page.
(9) old third creeping plant chief editor " the molecular biology basis is with clinical ", publishing house of Southeast China University, in February, 2000 front page, the 222nd page.
Claims (2)
1. one kind promotes hemopoietic stem cell proliferation and the synthetic alimentation composition of hemoglobin, it is characterized in that raw material and weight ratio are as follows: nucleotide 90～110, arginase 12 0～30, lysine 20～30, cysteine 10～20, glycine 25～35, histidine 20～30, lecithin 110～130, cephalin 50～70, vitamin E 0.4～0.6, vitamin C 5～7, folic acid 0.02～0.04, vitamin B
20.05～0.07, vitamin B
60.07～0.08, vitamin B
120.0001～0.0002, ferrum 0.5～1.5, zinc 0.5～0.7, manganese 0.4～0.6, lycium barbarum polysaccharide 14～16, Semen Vitis viniferae extract 14～16.
2. promotion hemopoietic stem cell proliferation according to claim 1 and the synthetic alimentation composition of hemoglobin is characterized in that raw material and weight ratio are as follows: nucleotide 100, arginase 12 5, lysine 25, cysteine 15, glycine 30, histidine 25, lecithin 120, cephalin 60, vitamin E 0.5, vitamin C 6, folic acid 0.03, vitamin B
20.06, vitamin B
60.06, vitamin B
120.0001, ferrum 1, zinc 0.6, manganese 0.5, lycium barbarum polysaccharide 15, Semen Vitis viniferae extract 15.
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