CN103142819A - Traditional Chinese medicine composition for preventing and treating cardiac muscle fibers or myocardial hypertrophy - Google Patents
Traditional Chinese medicine composition for preventing and treating cardiac muscle fibers or myocardial hypertrophy Download PDFInfo
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- CN103142819A CN103142819A CN2013100938544A CN201310093854A CN103142819A CN 103142819 A CN103142819 A CN 103142819A CN 2013100938544 A CN2013100938544 A CN 2013100938544A CN 201310093854 A CN201310093854 A CN 201310093854A CN 103142819 A CN103142819 A CN 103142819A
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Abstract
The invention discloses a traditional Chinese medicine composition for preventing and treating cardiac muscle fibers or myocardial hypertrophy. The traditional Chinese medicine composition is prepared from the following bulk pharmaceutical chemicals in parts by weights based on the traditional Chinese medicines: 50 to 30 parts of panax japonicus, 8 to 36 parts of fructus trichosanthis, 10 to 30 parts of kudzuvine root, 8 to 24 parts of ligusticum wallichii, and 6 to 28 parts of allium macrostemon. As the animal experiment and statistical analysis shown, after a rate subjected to cardiac muscle fibers or myocardial hypertrophy is given the traditional Chinese medicine composition, the full heart weight/body weight, cardiac ventricle weight/body weight, heart tissue inflammatory cells and cardiac muscle cell interstitial collagen are obviously reduced, the CVF (Collagen Volume Fraction) is obviously reduced, and therefore, that the composition has the effect of preventing and treating the cardiac muscle fibers or the myocardial hypertrophy is determined. The traditional Chinese medicine composition can be prepared into tablets, capsules, granules, oral liquid or injection together with pharmaceutically acceptable auxiliary materials.
Description
Technical field
The present invention is the clinical practice field of Chinese medicine, is mainly the application of a kind of Chinese medicine composition in control myocardial fibrosis or myocardial hypertrophy, the invention still further relates to simultaneously the preparation method of this Chinese medicine composition.
Background technology
Myocardial fibrosis or myocardial hypertrophy are a kind of remodeling ventricles that the heart long-term load occurs when overweight, except between myocardial cell connective tissue deposition, also follow the synthetic increase of cardiac muscle cell protein and cell volume to increase, have a strong impact on normal contraction and the diastolic function of heart.Myocardial fibrosis or myocardial hypertrophy are multiple cardiovascular system diseases, as hypertension, coronary heart disease, and common complication and the pathologic basis of valvular heart disease, congenital heart disease, myocardial inflammation etc.The myocardial fibrosis or the myocardial hypertrophy that continue will cause serious arrhythmia, heart failure.
The clinical medicine that can be used for treating myocardial fibrosis or myocardial hypertrophy has angiotensin-convertion enzyme inhibitor, aldosterone receptor antagonist, calcium channel road blocker, angiotensin receptor blocker, beta-blocker, matrix metallo-proteinase inhibitor, blockade of endothelin receptors agent etc.At present, in these medicines, only have angiotensin-convertion enzyme inhibitor to obtain certain clinical therapeutic efficacy, but act on limited, can not obtain the effect of very obvious resisting myocardial fibrillation or myocardial hypertrophy, other medicines there is no the clear evidence demonstration at present can improve myocardial fibrosis or myocardial hypertrophy, so lack at present with strong points and eutherapeutic medicine.Chinese medicine composition involved in the present invention has determined curative effect, and is safe, and action target spot is abundant, and side effect is little, cheap advantage.
Chinese patent CN 101780071A discloses the application of active ingredient of Chinese herbs osthole in preparation control myocardial fibrosis medicine on July 21st, 2010.Osthole can obviously reduce the heavy index of the heart, hydroxyproline content, CVF, reduces the fibrous tissue between myocardial cell.
Chinese patent CN102000095A discloses the application of asiaticoside in the medicine of preparation prevention or treatment myocardial fibrosis on April 6th, 2011.Asiaticoside has the effect of anti-spontaneous hypertensive rat (SHR) myocardial fibrosis, can obviously reduce whole-heartedly heavy, left ventricle is heavy, reduces intracardiac, adventitia and small artery myocardial collagen fraction by volume.
Summary of the invention
One of technical problem to be solved by this invention has been to invent myocardial fibrosis or patients with cardiac hypertrophy provides the Chinese medicine composition that can prevent and treat myocardial fibrosis damage or myocardial hypertrophy.
The Chinese medicine composition of control myocardial fibrosis provided by the invention or myocardial hypertrophy is prepared from by the crude drug of following weight parts: Rhizoma Panacis Japonici 5-20 part, Fructus Trichosanthis 8-24 part, Radix Puerariae 10-20 part, Rhizoma Chuanxiong 8-16 part, Bulbus Allii Macrostemonis 6-18 part.
Preferably, the weight portion of the above-mentioned Chinese medicine composition of the present invention is respectively: Rhizoma Panacis Japonici 10-20 part, Fructus Trichosanthis 12-24 part, Radix Puerariae 10-15 part, Rhizoma Chuanxiong 8-12 part, Bulbus Allii Macrostemonis 6-12 part.
Preferably, the weight portion of the above-mentioned Chinese medicine composition of the present invention is respectively: 15 parts of Rhizoma Panacis Japonicis, 24 parts of Fructus Trichosanthis, 12 parts of Radix Puerariaes, 10 parts of Rhizoma Chuanxiongs, 12 parts of Bulbus Allii Macrostemonis.
The above-mentioned Chinese medicine composition of the present invention is a kind of in tablet, capsule, granule, oral liquid or injection.
Preferably, the above-mentioned medicament of the present invention is mixture.
Chinese medicine composition of the present invention experimental results show that the effect that it has obvious resisting myocardial fibrillation or myocardial hypertrophy in body.
The present invention gets the ligation of male wistar rat underwent coronary and copies myocardial fibrosis or myocardial hypertrophy animal model, to studies show that of above-mentioned Chinese medicine composition:
(1) after myocardial fibrosis or myocardial hypertrophy model group rat give Chinese medicine composition of the present invention, obviously reduce heavy/body weight, ventricle weight/body weight whole-heartedly.
(2) myocardial fibrosis or myocardial hypertrophy model group rat HE dyeing finds in heart tissue, inflammatory cell infiltration is widely arranged; The cardiac muscle fiber fracture, arrangement disorder; Myocardium cell necrosis.After giving Chinese medicine composition of the present invention, the heart tissue inflammatory cell obviously reduces.
(3) a large amount of collagenic connective tissue hypertrophy are found in myocardial fibrosis or myocardial hypertrophy model group rat Masson dyeing.After giving Chinese medicine composition of the present invention, the myocardial cell interstitial collagen obviously reduces, and CVF obviously reduces.
Description of drawings
Fig. 1 is that after HE dyeing, the heart tissue pathology change, and wherein 1 is pseudo-operation group, and 2 is model group, and 3 is present composition high dose group.
Fig. 2 is that after Masson dyeing, the heart tissue pathology change, and wherein 1 is pseudo-operation group, and 2 is model group, and 3 is present composition high dose group.
Fig. 3 is the variation of TGF-β 1 after immunohistochemical staining, and wherein 1 is pseudo-operation group, and 2 is model group, and 3 is present composition high dose group.
The specific embodiment
According to following embodiment, the present invention may be better understood.Yet the described concrete material proportion of embodiment, process conditions and result thereof only are used for explanation the present invention and are not used in restriction protection scope of the present invention.After the content of having read the present invention's record, those skilled in the art can make various changes or modifications the present invention, and these equivalences change and modification falls into claim limited range of the present invention equally.
Following examples of the present invention Rhizoma Panacis Japonici used is the dry rhizome of Araliaceae Rhizoma Panacis Japonici Panax japonicus C.A.May.
Following examples of the present invention Fructus Trichosanthis used is the full fruit of cucurbitaceous plant Fructus Trichosanthis Trichosanthes kirilowii Maxim;
Following examples of the present invention Radix Puerariae used is the dry root of pulse family Herba Gelsemii Elegantis pueraria lobata (Willd.) Ohwir.
Following examples of the present invention Rhizoma Chuanxiong used is the dry rhizome of Umbelliferae Rhizoma Chuanxiong Ligusticum chuanxiong Hort..
Following examples of the present invention Bulbus Allii Macrostemonis used is the dry phosphorus stem of liliaceous plant Allium macrostemon Allium macrostemon Bunge;
Embodiment
Show resisting myocardial fibrillation or myocardial hypertrophy effect in the body of Chinese medicine composition of the present invention with experimental data.
1. tested medicine
Weighting raw materials 7 staggering amounts in proportion add respectively 50% alcohol reflux 3 times of 18 times of amounts, each 1.5 hours.Filter, merge extractive liquid, is evaporated to every milliliter and is equivalent to the lg crude drug.
2. laboratory animal
The Wiatar rat, male, body weight 250-300g, west, Shanghai pul-Bi Kai laboratory animal company limited provides [SCXK (Shanghai) 2008-0016].
3. experimental technique
3.1 the foundation of myocardial fibrosis or myocardial hypertrophy model
Be fixed on operating board after rats by intraperitoneal injection 10% chloral hydrate anesthesia (0.3mL100g-1).Open respirator (respiratory quotient is made as 1: 2 for 72 min-1 of respiratory frequency, tidal volume 18mL), insert from the rat mouth with tracheal intubation, rise and fall to rat chest consistent with the respirator frequency, illustrate and insert trachea.Left front breast unhairing, iodophor disinfection, scalpel cuts skin in the 3rd root bone place, separates subcutaneous tissue and muscle along grain of meat, and the 3rd of blunt separation and the 4th root spatium interosseum are torn pericardium, expose and extrude heart.Suture needle pin under the rat heart left auricle lower edge, the place goes out pin to pulmonary conus, and depth of needle is controlled at 0.1cm left and right, ligation ramus descendens anterior arteriae coronariae sinistrae.Observe left ventricular wall ischemic region cardiac muscle after ligation and bleach, ventricular wall motion weakens, and auricle is obviously congested, namely points out the ligation success.Successively close breast after hemostasis, extract endotracheal intubation, cleaning rat airway secretions is put into cage after it recovers autonomous respiration and regains consciousness.Every rat muscle injection penicillin of postoperative 20IU days-1, for three days on end.Pseudo-operation group rat heart arteria coronaria place's not ligation of threading, all the other operate same model group.
3.2 grouping administration
In 2 weeks after modeling, animal is divided at random in modeling: myocardial fibrosis or myocardial hypertrophy model group (hereinafter to be referred as model group), the large, medium and small dosage group of Chinese medicine composition (12g, 6g, the 3g crude drug/kg), positive drug Captopril group (50mg/kg).Add 6 groups altogether of pseudo-operation groups.Be administered once every day, administration volume 10ml/kg, 4 weeks of successive administration.Pseudo-operation group and model group give the equal-volume distilled water.After modeling the 42nd day, namely after administration the 28th day, last administration post processing animal.
3.3 index detects
Myocardial fibrosis refers to that in cardiac muscular tissue, collagen concentration significantly raises or collagen volume fraction (collagen volume fraction, CVF) be significantly higher than normal value, its principal character is that the fibroblast number increases and myocardial cell outer room matter collagen over-deposit.TGF-signal beta path is being brought into play pivotal role in the myocardial fibrosis that various cardiovascular disease cause.Myocardial hypertrophy is to show as inflammatory cell infiltration is widely arranged in heart tissue, cardiac muscle fiber fracture, arrangement disorder, myocardium cell necrosis.
The heavy index of the heart: core dirty, weigh, calculate heart/body weight and ventricle/body weight ratio.
The heart tissue hydroxyproline content detects: hydroxyproline is distinctive aminoacid in collagen, and its content can be used for analyzing the content of collagen protein in tissue.Take approximately 50-100mg of heart, measure hydroxyproline content in heart tissue.
The heart tissue pathological observation: 10% formalin is fixed, and carries out HE dyeing, and optical microphotograph Microscopic observation heart tissue structure changes.
Myocardial collagen fraction by volume: masson dyeing is the specific stain of collagen.Heart section masson dyeing, through Zessi Axioskop2 microscope images acquired, analyze and calculate masson stained positive (it is blue that collagen is) area percentage through Image-pro plus image processing software, be myocardial collagen fraction by volume (collagen volume fraction, CVF).Every section is chosen at random 5 visuals field and is done the image analysis, with the measured value of CVF average as this sample.CVF is larger, and the expression collagen content is more.
Heart tissue TGF-β 1 detects: adopt immunohistochemical method to detect the expression of TGF-β 1 in heart tissue.Images acquired, 5 visuals field are chosen in every section at random, images acquired, Image-pro plus image processing software automatic analysis calculates positive cell number, with the measured value of positive cell mean as this sample.
4. experimental result
4.1 the heavy index of the heart: heart/body weight of model group animal and ventricle/body weight ratio is pseudo-operation group high (P＜0.05～0.01) obviously.Compare with model group, Chinese medicine composition of the present invention can obviously reduce heart/body weight and ventricle/body weight value (P＜0.05), and myocardial hypertrophy is had good therapeutical effect.See Table 1.
The impact of table 1 Chinese medicine composition on the heavy coefficient of myocardial fibrosis/rat cardiac hypertrophy heart
Compare with puppet operation group
△ △Compare with model group p＜0.01
*P＜0.05,
*P＜0.01
4.2 heart tissue hydroxyproline content: model group animal hearts hydroxyproline in tissue and pseudo-operation group obviously increase, and after giving Chinese medicine composition of the present invention, in heart tissue, hydroxyproline content obviously reduces (P＜0.05～0.01).See Table 2.
The impact of table 2 Chinese medicine composition on myocardial fibrosis/rat cardiac hypertrophy CVF value, hydroxyproline content and TGF-β 1
Compare △ △ p＜0.01 with puppet operation group, compare with model group
*P＜0.05,
*P＜0.01
4.3 the heart tissue pathology change
HE stained microscopically is observed, and pseudo-operation group rat heart organizational structure marshalling has no fracture, degeneration, necrosis and inflammatory cell infiltration; Ventricular endocardium and adventitia no abnormality seen change; In model group rat heart tissue, inflammatory cell infiltration is widely arranged; The cardiac muscle fiber fracture, arrangement disorder; Myocardium cell necrosis.Chinese medicine composition group of the present invention can obviously reduce the lesion degree of animal pattern, reduces the necrosis of inflammatory cell infiltration and myocardial cell.(Fig. 1 is seen in HE dyeing).
Utilize Masson dyeing to the rat heart muscle tissue staining, it is blue that collagen is.Microscopically is observed, and pseudo-operation group rat heart muscle is organized as redness, has few part collagen to be blue; The model group rat heart muscle organizes red staining less, and collagen blue dyeing zone is larger, mainly is distributed in myocardial necrosis kitchen range limit (Fig. 2 is seen in Masson dyeing), shows in the local collagenic connective tissue hypertrophy of focus, and fibrosis occurs.Chinese medicine composition group of the present invention can obviously reduce the blue dyeing district, and namely myocardial collagen obviously reduces, and its CVF value obviously reduces (P＜0.05～0.01) than model group.See Table 2.
4.4 SABC TGF-β 1 expresses
Compare with puppet operation group, model group rat heart muscle tissue T GF-β 1 expresses significantly and raises, and sees Fig. 3, TGF-β 1 positive expression cell number significantly raise (p＜0.01), after giving Chinese medicine composition of the present invention, heart tissue TGF-β 1 expresses and significantly reduces (P＜0.01).See Table 2.
Above results suggest Chinese medicine composition of the present invention has obvious resisting myocardial fibrillation or myocardial hypertrophy effect, and its effect may be expressed relevant with reduction TGF-β 1.
Sum up: zoopery shows that compositions of the present invention has obvious resisting cardiac hypertrophy or myocardial fibrosis effect.Compositions of the present invention further also can with pharmaceutically acceptable adjuvant, make the medicine of the different dosage forms such as tablet, capsule, granule, oral liquid or injection.
Claims (3)
1. Chinese medicine composition of preventing and treating myocardial fibrosis or myocardial hypertrophy is characterized by said composition and is comprised of the crude drug of following weight parts: Rhizoma Panacis Japonici 5-30 part, Fructus Trichosanthis 8-36 part, Radix Puerariae 10-30 part, Rhizoma Chuanxiong 8-24 part, Bulbus Allii Macrostemonis 6-28 part.
2. the Chinese medicine composition of control myocardial fibrosis according to claim 1 or myocardial hypertrophy, the weight portion that it is characterized by each crude drug is respectively: Rhizoma Panacis Japonici 10-20 part, Fructus Trichosanthis 12-24 part, Radix Puerariae 10-15 part, Rhizoma Chuanxiong 8-12 part, Bulbus Allii Macrostemonis 6-12 part.
3. the Chinese medicine composition of control myocardial fibrosis according to claim 1 and 2 or myocardial hypertrophy, is characterized by said composition and pharmaceutically acceptable adjuvant, makes tablet, capsule, granule, oral liquid or injection.
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| CN105327172A (en) * | 2015-11-19 | 2016-02-17 | 王丽 | Myocardial hypertrophy resistant pharmaceutical composition as well as preparation method and application thereof |
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| CN101254266A (en) * | 2007-03-02 | 2008-09-03 | 段立新 | Cardiac and cerebral vascular disease treating medicine |
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| CN101254266A (en) * | 2007-03-02 | 2008-09-03 | 段立新 | Cardiac and cerebral vascular disease treating medicine |
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| 杨冬梅: "中药防治心肌肥厚的研究进展", 《2010年中国药学大会暨第十届中国药师周论文集》, 31 December 2010 (2010-12-31), pages 1 - 5 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105327172A (en) * | 2015-11-19 | 2016-02-17 | 王丽 | Myocardial hypertrophy resistant pharmaceutical composition as well as preparation method and application thereof |
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