CN101623432B - Application of jade lady variant decoction in preparing medicament for treating hyperthyrea symptom - Google Patents
Application of jade lady variant decoction in preparing medicament for treating hyperthyrea symptom Download PDFInfo
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Abstract
The invention discloses application of jade lady variant decoction in preparing a medicament for treating hyperthyrea symptom. The invention also discloses application of the jade lady variant decoction in preparing a medicament for treating hyperthyroid heart disease relevant to the hyperthyrea symptom. The jade lady variant decoction can be complementary with the prior chemical medicament in a hyperthyrea treatment mechanism, can be synergized with the chemical medicament in clinical application so as to reduce the consumption of the chemical medicament and possibly becomes a valuable substituent treatment means for patients who cannot tolerate the adverse reaction of the chemical medicament. The application provides new valuable experimental evidence for developing new Chinese medicament for treating the hyperthyrea symptom and the hyperthyroid heart disease relevant to the hyperthyrea symptom.
Description
Technical field
The present invention relates to the new medical usage of the classical compound recipe plus-minus of oral Chinese medicine yun.
Background technology
Hyperthyroidism is called for short " hyperthyroidism ", generally is meant owing to a series of syndromes such as the caused basal metabolic rate of thyroid self pathological changes (BMR) increase, autonomic nervous system is not normal.Hyperthyroidism is because a variety of causes causes that thyroid hormone secretion increases; Cause the irritability of body multisystem to increase and hypermetabolic clinical syndrome, its clinical manifestation mainly contains irritated irritability, cardiopalmus hyperhidrosis, be prone to famine become thin, point tremble, thyromegaly or exophthalmos etc.
Hyperthyroidism is one of frequently-occurring disease, difficult treatment of modern society, serious harm modern healthy, at present; Used ATD is main with thiourea in clinical; Its mechanism of action is for suppressing the synthetic of thyroxin, in the clinical use onset slower, the course of treatment is longer; And side effect is many, even has the part patient to tolerate.
Along with the increase of society, operating pressure, the quickening of rhythm of life, hyperthyroid sickness rate obviously increases.Epidemiological study finds that the hyperthyroid total incidence of China is unexpectedly up to 3%.Because the metabolism rate increases, hyperthyroidism patient has that To Be Protected from Heat, hyperhidrosis, nervous, heart rate is fast, polyphagia, become thin, symptom such as times of defecation increases; Because sympathetic excitability increases, also normal performance have nervousness, passionnate, hands is trembled, insomnia etc.Patient about 90% increases with thyroid, and part patient also has expophthalmos.Hyperthyroidism patient's 5%～10% a series of cardiac symptoms such as arrhythmia, cardiac enlargement, heart failure occur on the sick basis of hyperthyroidism, thyrotoxic heart disease occurs.There are some researches show that hyperthyroidism patient's sickness rate is also continuing increase.
Hyperthyroidism does not have corresponding name of disease record in traditional Chinese medicine ancient books, according to its main clinical manifestation, this disease belongs to categories such as the traditional Chinese medical science " liver-fire ", " goiter ".Along with the modern times to the deepening continuously of hyperthyroidism research, more and more scholars thinks that stimulation is to cause hyperthyroid main pathogenic factor to natural endowment not enough (the plain body deficiency of YIN) with feelings will.To hyperthyroid pathogenesis, there is the scholar to stress that this disease is " being the center with the stagnation of liver-QI, relevant with the five internal organs imbalance "; And think " imbalance that is formed at internal organs of phlegm-turbidity and blood stasis blood; though be the center with the stagnation of liver-QI, but it is all dirty to have influence on cardiopulmonary spleen kidney ", therefore hyperthyroid pathogenic characteristic belongs to " deficiency in origin and excess in superficiality "; With " Liver and kidney heart spleen loses empty " is basis, and " stagnation of liver-QI gastric heat, transformation of fire and occurrence of wind syndrome, the expectorant stasis of blood are stagnated " is mark.Also have the scholar to think that hyperthyroid pathogenesis emphasis is a deficiency in origin and excess in superficiality, deficiency in origin is main with deficiency of qi and yin, mark real for scorching, expectorant is turbid and blood stasis is main.Their early stage is many with conscience fire stagnation (prosperous), and scorching flourishing, it is main burning in cloudy Tianjin; Disease is for a long time then with impairment of both QI and YIN, and hyperactivity of fire caused by deficiency of YIN is a main feature.Although opinions vary in each family, the pathogenesis of hyperthyroidism always be unable to do without the very crux of " deficiency in origin and excess in superficiality ", and deficiency in origin be its most basic foothold with the deficiency of YIN always, and it is main marking actually, blood stasis turbid with depressed, stagnated fire, expectorant.The traditional Chinese medical science is then many from pathogenesis in clinical treatment, giving consideration to both the incidental and fundamental, Therapeutic Method such as adopt supplementing QI and nourishing YIN, regulate the flow of vital energy, reduce phlegm, invigorate blood circulation.
Through discovering, many single medicinal materials such as Carapax et Plastrum Testudinis, Radix Gentianae, the Rhizoma Anemarrhenae, the Radix Rehmanniae etc. all have the T that certain reduction hyperthyroidism animal model raises
3, T
4Effect, and can alleviate because of the caused various symptoms of hyperthyroidism.More scholar is then from herbal mixture; With effective compound recipe in clinical; Like compound recipe hyperthyroidism capsule, the wart that disappears granule, high Xinning capsule etc.; Its drug effect to experimental hyperthyroidism animal model is inquired in the research that experimentizes, so that some new foundations are provided for the hyperthyroidism treatment.The hyperactivity of fire caused by deficiency of YIN body constitution of scholar from the hyperthyroidism patient is more arranged; Study the essence place of its syndrome of hyperactivity of fire due to deficiency of YIN; Think that hyperthyroidism hyperactivity of fire caused by deficiency of YIN and sympathetic-adrenal medulla function, cAMP and gastrin level and immune system, trace element, hemodynamics etc. all have substantial connection, thereby thinking is provided for hyperthyroid traditional Chinese medical science classification therapy and Chinese medicine antithyroid Mechanism Study hyperactivity.
The plus-minus yun is that the well-known doctor Wu of the Qing Dynasty brings up the logical name side in " Wenbing Tiaobian, Detailed Analysis of Epidemic Warm Diseases " of show, entirely just by Gypsum Fibrosum, the Rhizoma Anemarrhenae, Radix Scrophulariae, the Radix Rehmanniae, Radix Ophiopogonis five kinds of Chinese medicine form, function clearing qi and cooling blood, nourshing Yin and drynsessmoistening prescription can be used for treating the diseases such as thirsty, rapid pulse of lunar epidemic febrile disease.This side is that the yun sanction from Jing-Yue Complete Works forms; Have another name called yun and go the Radix Achyranthis Bidentatae Radix Rehmanniae Preparata to add medicaments of radix rehmanniae, figwort side, the sweet cold YIN nourishing of the Rhizoma Anemarrhenae, the Radix Rehmanniae, Radix Ophiopogonis is closed with the clearing heat with pungent and cool-natured drugs of Gypsum Fibrosum by full side; Again with the removing pathogenic heat from blood and toxic substance from the body of Radix Scrophulariae, the effect of playing YIN nourishing, heat clearing away, detoxifcation, removing heat from blood altogether.
Gypsum Fibrosum, acrid-sweet flavor attaches to the lung and stomach meridians in property Great Cold, and granulation promoting is quenched the thirst, is restrained in function clearing away heat-fire, relieving restlessness." not Lu " meaning: " removing seasonal epidemic pathogens headache fever of the body, the big heat of three warmers, skin heat, heat of the diaphragm in the intestines and stomach ... " is clinical clearing away heat-fire key medicine commonly used.Modern pharmacological research shows that Gypsum Fibrosum has heating significantly separates thermal effect, and can alleviate the caused thirsty state of heating.The Rhizoma Anemarrhenae, bitter but sweet flavor, cold in nature, return lung, stomach, kidney channel, function clearing away heat-fire, nourshing Yin and drynsessmoistening prescription." herbal classic " cloud: " main quenching one's thirst pined for, and removes pathogen, limbs edema, following water, tonifying for the deficiency, QI invigorating." modern pharmacology experiment showed, that Rhizoma Anemarrhenae main component Sarsasapogenin can make rat raises due to the thyroxine liver, kidney, mucous membrane of small intestine Na
+-K
+-ATP enzyme recovers normal level, thereby heat production is reduced, and realizes refrigeration function.Other has relevant report; Hyperthyroidism model beta receptor-cAMP system significantly strengthens the reactive of beta receptor agonist isoproterenol; Kidney beta receptor maximum binding capacity also significantly increases, and Rhizoma Anemarrhenae water extract can make both reduce to normal level, but the affinity of beta receptor is not had influence; And the Rhizoma Anemarrhenae also can reduce the oxygen consumption of hyperthyroidism animal pattern.Radix Scrophulariae, bitter but sweet flavor is salty, and is cold in nature, returns lung, stomach, kidney channel, function clearing away heat and cooling blood, YIN nourishing detoxifcation." not Lu " carries: " following water ends excessive thirst, the neck nuclear down that looses, carbuncle." modern pharmacology experiment discovery, Radix Scrophulariae can strengthen the hypoxia-bearing capability of experiment mice, and simultaneously, its spontaneous activity to mice also has certain inhibitory action.The Radix Rehmanniae, sweet-bitter flavor, cold in nature, GUIXIN, liver, lung meridian, function clearing away heat and cooling blood, YIN nourishing and the production of body fluid promoting." pearl sac " has cloud: " the kidney invigorating water is Kidney-Yin for removing heat from blood, hemopoietic." modern pharmacological research experiment shows; fresh rehmannia root juice, Radix Rehmanniae decocting fluid power obviously strengthen the spleen lymphocyte alkali phosphatase ability to express of class deficiency of YIN mice that thyroxine brings out; can also strengthen the inductive spleen lymphocyte conversion of ConA, point out it that bone-marrow-derived lymphocyte, T lymphocyte function are had facilitation.Radix Ophiopogonis, sweet and slightly bitter taste, cold nature, GUIXIN, lung, kidney channel, function nourishing YIN and moistening the lung, reinforcing stomach reg fluid, relieving restlessness clears away heart-fire." not Lu " carries: " treat the asthenia exopathogenic heat, dry mouth is thirsty." modern experimentation shows, with the injection of Radix Liriopes decoction alcohol precipitation method preparation mice carried out in the anoxia enduring experiment, the mice hypoxia endurance time prolongs 15.4% and 31.7% respectively under normal pressure; Under reduced pressure, also significant prolongation of mice time-to-live.
Do not see in the document that the plus-minus yun has the hyperthyroid report of control.
Summary of the invention
Technical problem to be solved by this invention is to propose the new purposes of classics side's plus-minus yun in pharmacy.
The present invention relates to add and subtract the purposes of yun in the hyperthyroid medicine of preparation treatment.
The invention still further relates to the purposes of plus-minus yun in the medicine of the preparation treatment hyperthyroid heart disease relevant with hyperthyroidism.
The present invention is an object with classical ancient prescription plus-minus yun; Adopt domestic and international academia extensive use the modeling of subcutaneous injection levothyroxine sodium and observe methods such as iodine uptake rate and thyrotropin experiment, reach reliable pharmacodynamics detection means; By techniques well known, mouse subcutaneous injection dextrothyroxine sodium 350 μ g/kg/d.Modeling and administration are carried out simultaneously, every day 1 time.Successive administration 8d observes the influence of plus-minus yun to hyperthyroidism model mice heart rate, spontaneous activity, and successive administration 11d observes and inhales
125The variation that I leads, successive administration 12d observes oxygen consumption, T
3, T
4Variation, intramuscular injection thyrotropin (thyrotropin) 1IU measures iodine uptake rate.
The present invention tests discovery: oral plus-minus yun granule can be alleviated the hyperthyroidism animal pattern symptom that loses weight; Its heart rate that slows down reduces the cardiac weight index, and can reduce the spontaneous activity of animal pattern; Reduce oxygen consumption, reduce serum T 3, T4 level in the animal pattern body.
Experimental result of the present invention shows: the plus-minus yun can be alleviated the clinical symptoms of hyperthyroidism; How moving like agitation, heart rate is accelerated, metabolism increases, loses weight etc.; Compare with model group, positive drug thiamazole group and plus-minus yun mice body weight are apparently higher than model group (P＜0.05); The cardiac weight index, heart rate, spontaneous activity, oxygen consumption, serum T
3, T
4Horizontal significance reduces (P＜0.05), and then produces the hyperthyroid effect of improvement.
Experimental result of the present invention confirms: the plus-minus yun has the obvious suppression effect to experimental hyperthyroidism; The symptom performance of hyperthyroidism animal model can be obviously improved, and the intravital thyroxine level of hyperthyroidism animal pattern can be significantly reduced.Its mechanism of action possibly mainly be the release through the effect of antagonism thyroxin or inhibition thyroxin, thereby improves the various clinical manifestations of hyperthyroidism, reduces thyroid hormones level.Therefore; The plus-minus yun can complement each other with existing chemicals on hyperthyroid treatment mechanism; Can be collaborative mutually in clinical practice with chemicals; To reduce the consumption of chemicals,, also possibly become valuable replacement therapy means simultaneously to tolerating the patient of chemical adverse effect.Therefore, the present invention provides new valuable experimental basis for the new Chinese medicine exploitation of treatment hyperthyroidism, the hyperthyroid heart disease relevant with hyperthyroidism.
In addition, the Chinese medicine of the five flavours of plus-minus in the yun side be all inexpensive, be easy to get, and do not see obvious acute toxicity.Rhizoma Anemarrhenae total saponins is as one of effective ingredient in the plus-minus yun; In range of doses, also has antithyroid hyperfunctioning effect to a certain degree, as alleviating the symptom that the hyperthyroidism the weight of animals alleviates; Decreased heart rate reduces spontaneous activity etc.
The specific embodiment
Below in conjunction with embodiment the present invention is described further.
Embodiment 1
1. add and subtract yun antithyroid hyperfunctioning experimental study of effect
1.1 the preparation of experiment medicine
The plus-minus yun is formed and adult's dosage every day: Gypsum Fibrosum 30g, Rhizoma Anemarrhenae 12g, Radix Scrophulariae 12g, Radix Rehmanniae 18g, Radix Ophiopogonis 18g.The prepared slices of Chinese crude drugs are supported and hall pharmaceutcal corporation, Ltd available from Shanghai.
Granule after present embodiment experiment institute medicament is concentrated for plus-minus yun water decoction process, vacuum drying etc. handled, this granule is provided by Shanghai Univ. of Traditional Chinese Medicine's science and technology experimental center preparation, contains the 2.7g crude drug in the 1g granule approximately.
1.2 other medicines
The thiamazole sheet, Beijing Taiyang Pharmaceutical Co., Ltd., lot number: 060501.Levothyroxine sodium (L-Thyroxine Sodium salt), U.S. sigma company, lot number: WA13381.
1.3 reagent
Iodine [
125I] 3 (T
3) the radioimmunoassay, RIA medicine box; Iodine [
125I] thyroxine (T
4) the radioimmunoassay, RIA medicine box, all purchase pul great achievement bio tech ltd in Beijing.Na
125I solution, Shanghai Univ. of Traditional Chinese Medicine's Nuclear Medical Laboratory.Thyrotropin (Thyrotropic hormone from BovinePituitary), U.S. sigma company, lot number: 027K0726.
2. experimental apparatus and equipment
The ECG-92C electrocardiograph, Shanghai Photoelectricity Medical electron Instrument Co., Ltd..SN-682 radioimmunity gamma counter, Shanghai Atomic Nucleus Inst., Chinese Academy of Sciences's day is encircled instrument plant.The multi-functional mice autonomic activities of YLS-1A monitor, Shandong Academy of Medical Sciences equipment station.Mouse core electric induction box is provided by experiment Chinese medicine teaching and research room of Shanghai Univ. of Traditional Chinese Medicine.The CY-3 oxygen analyser, Shanghai China light instrument and meter factory.
3. laboratory animal
The KM mice, 20～30 grams, Shanghai Slac Experimental Animal Co., Ltd., credit number: SCXK (Shanghai) 2007-0005.
4. experimental technique
4.1 animal divides into groups
Get 72 of mices (male and female half and half), body weight 20～30g is divided in blank group, model control group, positive drug (thiamazole) group, plus-minus yun low dose group, the plus-minus yun 6 groups of dose groups and plus-minus yun high dose group, 12 every group at random.
4.2 modeling and medication
Modeling: except that the blank group, all the other respectively organize subcutaneous injection dextrothyroxine sodium 350 μ g/kg body weight every day.The blank group is injected the normal saline of same dosage by body weight.Administration: irritate stomach and give the low 2.17g/kg of thiamazole group 10mg/kg/d plus-minus yun, middle 4.33g/kg, high 8.66g/kg, model and blank give isopyknic normal saline.
4.3 index determining and method
4.3.1 the plus-minus yun is to the influence of hyperthyroidism model mice outward appearance behavior
The omnidistance also overall condition of record mice of observing of experimental session comprises the mental status, hair color variation, behavioral activity of mice etc.
4.3.2 the plus-minus yun is to the influence of hyperthyroidism model mice body weight
Measure and write down the body weight of respectively organizing mice before the experiment; Measurement and record mice body weight are 1 time next day of in the experimentation, modeling and administration, continuous 12 days; After last modeling, administration; Water 12h is can't help in fasting, measures and writes down and respectively organize the mice body weight, calculates the difference between the preceding body weight value of measuring of last body weight value of measuring and experiment.
4.3.3 the plus-minus yun is to the exponential influence of hyperthyroidism model mice cardiac weight
Modeling and administration, continuous 9 days, after last modeling, administration, water 12h was can't help in fasting, measured and write down and respectively organize the mice body weight, got its heart, and the weight of mouse heart respectively organized in record, calculates cardiac index.
4.3.4 the plus-minus yun is to the influence of hyperthyroidism model mice heart rate
Modeling, administration, continuous 8 days, in after last modeling, the administration about 3h, under the mice waking state, mice is placed the telepathy box, induction box connects electrocardiograph simultaneously, traces the II lead electrocardiogram with electrocardiograph.
4.3.5 the plus-minus yun is to the influence of hyperthyroidism model mice spontaneous activity
[1]
Modeling, administration, continuous 8 days, 60min after last administration, modeling placed toy autonomic activities analyzer with mice, adapted to 5min, write down the number of times of the interior mice autonomic activities of 10min after this.
4.3.6 the plus-minus yun is to the influence of hyperthyroidism model mice oxygen consumption
Get each 60 of female, male mices, be divided into that blank group, model control group, positive drug group, plus-minus yun are low, in the plus-minus yun and the plus-minus yun high 6 groups, 10 every group.Modeling, administration, continuous 12 days, after last modeling, administration, about 3h mice is enclosed within the 500ml bottle, measure also record female mice 30min, oxygen content in the bottle behind the male mice 20min is respectively organized the difference of the oxygen consumption of mice.
4.3.7 the plus-minus yun is to hyperthyroidism model mice serum T
3, T
4Influence
Modeling, administration, continuous 12 days, after last modeling, administration, water 12h was can't help in fasting, and eyeball is got blood, adopts the RIA method to measure the T in the serum
3, T
4Content.
4.3.8 the plus-minus yun is inhaled the hyperthyroidism model mice
125The influence that I leads
Modeling, administration, continuous 11 days, 1h began to all animal lumbar injection Na after the last administration
125(so the about 30g of female mice average weight is every injection 0.3 μ Ci for I 0.1 μ Ci/10g body weight; So the about 40g of male mice average weight is every injection 0.4 μ Ci), behind the 24h, put to death animal, peel off, extract whole thyroid, with SN-682 radioimmunity gamma counter, measure its radioactivity, simultaneously the bioassay standard source
125The radioactivity of I calculates thyroid and inhales
125I leads.
4.3.9 thyrotropin experiment
Get 30 of mices (male and female half and half), be divided into model group, one group of plus-minus yun high dose, two groups of plus-minus yun high doses, 10 every group.Every day subcutaneous injection dextrothyroxine sodium 350 μ g/kg body weight, one group and two groups of high dose is all irritated stomach plus-minus yun 8.66g/kg, model group gives distilled water.Modeling as stated above, administration on 10th, gave plus-minus yun high dose two treated animal intramuscular injection thyrotropin 1IU after 9 days, then distinguished the isometric normal saline of intramuscular injection for other two groups.Behind the 24h, lumbar injection Na
125I behind the 24h, puts to death animal again, calculates iodine uptake rate.
5. statistical method
All The data " mean ± standard deviation (x ± S) " expression, relatively adopt one factor analysis of variance between many groups, relatively adopt the t check between two groups, inspection level is 0.05.
6. experimental result
6.1 the plus-minus yun is to the influence of hyperthyroidism model mice outward appearance behavior
In the experimentation, blank group mice mental status, active situation, the equal no abnormality seen of hair color gloss.The modeling of model group mice began to occur dysphoria on the 4th day, is prone to enrage, and with blank group mice the withered phenomenon of obvious hair color was arranged relatively.Treatment group mice also has the withered phenomenon of slight hair color, but than the model group mild symptoms, and plus-minus yun administration group is than the model group mice relatively, and it shows rest state to a certain degree, and especially the performance of high dose group mice is more obvious.
6.2 the plus-minus yun is to the influence of hyperthyroidism model mice body weight
Before the treatment (before administration, the modeling), each organizes the mice weight ratio than there was no significant difference (P＞0.05).After the treatment, compare with the blank group, model group mice body weight is starkly lower than the blank group, and both have extremely significant difference (P＜0.01); Compare with model group, positive drug thiamazole group and plus-minus yun high dose group mice body weight are apparently higher than model group, and its difference also has significance (P＜0.05).Body weight carries out comparing between each group before the treatment back-treatment.Compare with the blank group, model group mice weight increase is starkly lower than the blank group, and both relatively have extremely significant difference (P＜0.01); Compare with model group, thiamazole group and the middle and high dose groups mice of plus-minus yun weight increase are apparently higher than model group, and its difference also has significance (P＜0.05).(seeing table 2-1)
Table 2-1 plus-minus yun is to the influence of hyperthyroidism mice body weight (x ± S)
Annotate: compare ##P＜0.01 with the blank group; Compare with model group, ▲ P＜0.05, ▲ ▲ P＜0.01
6.3 the plus-minus yun is to the exponential influence of hyperthyroidism model mice cardiac weight
Compare with the blank group, model group mouse heart index obviously increases, and both have extremely significant difference (P＜0.001).Compare with model group, dose groups mouse heart index obviously reduces in the plus-minus yun, and both have significant difference (P＜0.05); Plus-minus yun high dose group mouse heart index also obviously reduces, and diversity extremely significantly (P＜0.01) between the model group.(seeing table 2-2)
Table 2-2 plus-minus yun is to the influence of hyperthyroidism mouse heart ponderal index (x ± S)
Annotate: compare ###P＜0.001 with the blank group; Compare with model group, ▲ P＜0.05, ▲ ▲ P＜0.01, ▲ ▲ ▲ P＜0.001
6.4 the plus-minus yun is to the influence of hyperthyroidism model mice heart rate
Compare with the blank group, model group mice heart rate is obviously accelerated, and both have significant difference (P＜0.05).Compare with model group, the basic, normal, high dose groups mice of plus-minus yun heart rate obviously slows down, and both also have significant difference (P＜0.05).(seeing table 2-3)
Table 2-3 plus-minus yun is to the influence of hyperthyroidism mice heart rate (x ± S)
Annotate: compare #P＜0.05 with the blank group; Compare ▲ P＜0.05 with model group
6.5 the plus-minus yun is to the influence of hyperthyroidism model mice spontaneous activity
Compare with the blank group, model group spontaneous activity in mice showed increased, both have significant difference (P＜0.05).Compare with model group, plus-minus middle and high dose groups of yun and positive drug thiamazole group spontaneous activity in mice obviously reduce, and both also have significant difference (P＜0.05).(seeing table 2-4)
Table 2-4 plus-minus yun is to the influence of hyperthyroidism spontaneous activity in mice (x ± S)
Annotate: compare #P＜0.05 with the blank group; Compare ▲ P＜0.05 with model group
6.6 the plus-minus yun is to the influence of hyperthyroidism model mice oxygen consumption
(1) compare with the blank group, female mice model group oxygen consumption obviously increases, and both have extremely significant difference (P＜0.001).Compare with model group, the dose groups oxygen consumption obviously reduces in the female mice plus-minus yun, and both have significant difference (P＜0.05); Thiamazole group, plus-minus yun high dose group oxygen consumption also obviously reduce, and diversity extremely significantly (P＜0.01) between the model group.(seeing table 2-5-1)
(2) compare with the blank group, male mice model group oxygen consumption obviously increases, and both have extremely significant difference (P＜0.01).Compare with model group, the dose groups oxygen consumption obviously reduces in the male mice plus-minus yun, and both have significant difference (P＜0.05); Thiamazole group, plus-minus yun high dose group oxygen consumption also obviously reduce, and diversity extremely significantly (P＜0.01) between the model group.(seeing table 2-5-2)
Table 2-5-1 plus-minus yun is to the influence of female hyperthyroidism mice oxygen consumption (x ± S)
Annotate: compare ###P＜0.001 with the blank group; Compare with model group, ▲ P＜0.05, ▲ ▲ P＜0.01, ▲ ▲ ▲ P＜0.001
Table 2-5-2 plus-minus yun is to the influence of male hyperthyroidism mice oxygen consumption (x ± S)
Annotate: compare ##P＜0.01 with the blank group; Compare with model group, ▲ P＜0.05, ▲ ▲ P＜0.01
6.7 the plus-minus yun is to hyperthyroidism model mice serum T
3, T
4Influence
(1) compares model group mice serum T with the blank group
3Level obviously increases, and both have extremely significant difference (P＜0.001).Compare plus-minus middle and high dose groups of yun and thiamazole group serum T with model group
3Level also obviously reduces, and both have extremely significant difference (P＜0.01).(seeing table 2-6-1)
(2) compare model group mice serum T with the blank group
4Level obviously increases, and both have extremely significant difference (P＜0.001).Compare dose groups serum T in the plus-minus yun with model group
4Level obviously reduces, and both have significant difference (P＜0.05); Thiamazole group, plus-minus yun high dose group serum T
4Level also obviously reduces, and diversity extremely significantly (P＜0.01) between the model group.(seeing table 2-6-2)
Table 2-6-1 plus-minus yun is to hyperthyroidism mice T
3Influence (x ± S)
Annotate: compare ###P＜0.001 with the blank group; Compare with model group, ▲ ▲ P＜0.01, ▲ ▲ ▲ P＜0.001
Table 2-6-2 plus-minus yun is to hyperthyroidism mice T
4Influence (x ± S)
Annotate: compare ###P＜0.001 with the blank group; Compare with model group, ▲ P＜0.05, ▲ ▲ P＜0.01, ▲ ▲ ▲ P＜0.001
6.8 the plus-minus yun is inhaled the hyperthyroidism model mice
125The influence that I leads
Compare with the blank group, the model group mice inhales
125I leads obviously and reduces, and both have extremely significant difference (P＜0.001).Compare with model group, thiamazole group mice inhales
125It is more obvious that I leads reduction, and both have extremely significant difference (P＜0.001); And each its suction of administration group of plus-minus yun
125I leads with model group and compares, also decrease to some degree, but the difference between them does not have the significance meaning.(seeing table 2-7)
Table 2-7 plus-minus yun is inhaled the hyperthyroidism mice
125The influence that I leads (x ± S)
Annotate: compare ###P＜0.001 with the blank group; Compare with model group, ▲ ▲ ▲ P＜0.00
6.9 thyrotropin experiment
One group of high dose is compared its suction with model control group
125I leads decrease to some degree, but its difference does not have significance (P=0.157); Two groups of high doses are compared its suction for one group with high dose
125I leads significance and raises, and significant difference (P＜0.01) is arranged between the two.(seeing table 2-8)
The experiment of table 2-8 thyrotropin (x ± S)
Annotate: compare * * P＜0.01 for one group with high dose
Embodiment 2
Rhizoma Anemarrhenae total saponins is to the experimentation of hyperthyroidism model mice influence.
1. medicine and reagent
1.1 medicine
Rhizoma Anemarrhenae total saponins, purity＞50% is provided by pharmacology teaching and research room of Shanghai The 2nd Army Medical College.The thiamazole sheet, Beijing Taiyang Pharmaceutical Co., Ltd., lot number: 060501.Levothyroxine sodium (L-Thyroxine Sodiumsalt), U.S. sigma company, lot number: WA13381.
1.2 reagent
T
4The radioimmunoassay, RIA medicine box, PLA General Hospital Science and Technology Development Center, lot number: 20070330.
2. experimental apparatus and equipment
The ECG-92C electrocardiograph, Shanghai Photoelectricity Medical electron Instrument Co., Ltd..SN-682 radioimmunity gamma counter, Shanghai Atomic Nucleus Inst., Chinese Academy of Sciences's day is encircled instrument plant.The multi-functional mice autonomic activities of YLS-1A monitor, Shandong Academy of Medical Sciences equipment station.Mouse core electric induction box is provided by experiment Chinese medicine teaching and research room of preclinical medicine institute of Shanghai Univ. of Traditional Chinese Medicine.
3. laboratory animal
The KM mice, 20～30 grams, Shanghai Slac Experimental Animal Co., Ltd., credit number: SCXK (Shanghai) 2007-0005.
4. experimental technique
4.1 animal divides into groups
Get 60 of KM (male and female half and half), body weight 20～30g is divided in blank group, model control group, positive drug (thiamazole) group, Rhizoma Anemarrhenae total saponins low dose group, the Rhizoma Anemarrhenae total saponins 6 groups of dose groups and Rhizoma Anemarrhenae total saponins high dose group, 10 every group.
4.2 modeling and medication
Modeling: except that the blank group, all the other respectively organize subcutaneous injection dextrothyroxine sodium 350 μ g/kg body weight every day.The blank group is injected the normal saline of same dosage by body weight.Administration: irritate stomach and give the thiamazole group by 10mg/kg/d, the basic, normal, high dose groups of timosaponin is pressed 50mg/kg/d body weight, 100mg/kg/d body weight, 200mg/kg/d respectively every day, and blank group and model group give distilled water.
4.3 index determining and method
4.3.1 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice outward appearance behavior
The omnidistance also overall condition of record mice of observing of experimental session comprises the mental status, hair color variation, behavioral activity of mice etc.
4.3.2 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice body weight
Measure and write down the body weight of respectively organizing mice before the experiment; Measurement and record mice body weight are 1 time next day of in the experimentation, modeling, administration, every day 1 time; Continuous 9 days; After last modeling, the administration, measure and write down and respectively organize the mice body weight, calculate the difference between the preceding body weight value of measuring of last body weight value of measuring and experiment then morning next day.
4.3.3 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice heart rate
Modeling, administration, continuous 11 days, after last modeling, administration,, mice is placed the telepathy box at the mice waking state, induction box connects electrocardiograph simultaneously, traces the II lead electrocardiogram with electrocardiograph, calculates through electrocardiogram then and respectively organizes the mice heart rate.
4.3.4 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice spontaneous activity
[1]
Modeling, administration, continuous 7 days, 60min after last administration, modeling placed toy autonomic activities analyzer with each group mice, and at first adaptability is placed 5min, then the number of times of mice autonomic activities in the opening entry 10min.
4.3.5 Rhizoma Anemarrhenae total saponins is to hyperthyroidism model mice serum T
4Influence
Modeling, administration, continuous 11 days, after last modeling, administration, water 12h was can't help in fasting, and eyeball is got blood, and the centrifugal 10min of 3000r/min leaves and takes serum, adopts radioimmunoassay, RIA (RIA) method to measure the T in the serum
4Content.
5. statistical method
All The data " mean ± standard deviation (x ± S) " expression, relatively adopt one factor analysis of variance between many groups, relatively adopt the t check between two groups, inspection level is 0.05.
6. experimental result
6.1 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice outward appearance behavior
In the experimentation, blank group mice mental status, active situation, the equal no abnormality seen of hair color gloss.The modeling of model group mice began to occur dysphoria on the 4th day, is prone to enrage, and relatively the withered phenomenon of hair color is obvious with blank group mice, and timosaponin medication group and model group mice are relatively, and ergasias such as its dysphoria change and obviously alleviate.
6.2 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice body weight
Compare with the blank group, model group mice weight increase is starkly lower than the blank group, and both relatively have significant difference (P＜0.05).Compare with model group, low, the middle dose groups mice of positive drug thiamazole group and timosaponin weight increase is apparently higher than model group, and its difference also has significance (P＜0.05).Explain that model group mice body weight obviously reduces, and low, the middle dosage of thiamazole and timosaponin can make the reduction of hyperthyroidism mice body weight alleviate to some extent.(seeing table 1-1)
Table 1-1 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism mice body weight (x ± S)
Annotate: compare #P＜0.05 with the blank group; Compare ▲ P＜0.05 with model group
6.3 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice heart rate
Compare with the blank group, model group mice heart rate is obviously accelerated, and both have significant difference (P＜0.05).Compare with model group, dose groups mice heart rate obviously slows down in the timosaponin, and both also have significant difference (P＜0.05).Prompting hyperthyroidism model mice heart rate is obviously accelerated, and middle dosage timosaponin can be alleviated the symptom that hyperthyroidism mice heart rate is accelerated to a certain extent.(seeing table 1-2)
Table 1-2 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism mice heart rate (x ± S)
Annotate: compare #P＜0.05 with the blank group; Compare ▲ P＜0.05 with model group
6.4 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism model mice spontaneous activity
Compare with the blank group, model group spontaneous activity in mice showed increased, both have significant difference (P＜0.05).Compare with model group, its spontaneous activity of dose groups mice obviously reduces in the timosaponin, and both also have significant difference (P＜0.05).Explain that its spontaneous activity of model group mice obviously increases, and middle dosage timosaponin can make its spontaneous activity obviously reduce, dosage possibly have the effect that improves clinical manifestations such as hyperthyroidism mice restlessness in the prompting timosaponin.(seeing table 1-3)
Table 1-3 Rhizoma Anemarrhenae total saponins is to the influence of hyperthyroidism spontaneous activity in mice (x ± S)
Annotate: compare #P＜0.05 with the blank group; Compare ▲ P＜0.05 with model group
6.5 Rhizoma Anemarrhenae total saponins is to hyperthyroidism model mice serum T
4Influence
Compare model group mice serum T with the blank group
4Level significantly raises, and both have extremely significant difference (P＜0.001).Compare dose groups mice serum T in positive drug thiamazole group and the timosaponin with model group
4Level obviously reduces, and its difference has significance (P＜0.05).Its serum T of prompting hyperthyroidism model mice
4Level significantly raises, and positive drug thiamazole and middle dosage timosaponin can reduce the T of hyperthyroidism mice
4Level.(seeing table 1-4)
Table 1-4 Rhizoma Anemarrhenae total saponins is to hyperthyroidism mice serum T
4Influence (x ± S)
Annotate: compare ###P＜0.05 with the blank group; Compare with model group, ▲ ▲ ▲ P＜0.001; ▲ P＜0.05
Claims (2)
1. Wu brings up the logical application of plus-minus yun in the medicine of preparation treatment hyperthyroidism in " Wenbing Tiaobian, Detailed Analysis of Epidemic Warm Diseases " of showing.
2. Wu brings up the logical application of plus-minus yun in the medicine of the preparation treatment hyperthyroid heart disease relevant with hyperthyroidism in " Wenbing Tiaobian, Detailed Analysis of Epidemic Warm Diseases " of showing.
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