CN103142819B - 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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- CN103142819B CN103142819B CN201310093854.4A CN201310093854A CN103142819B CN 103142819 B CN103142819 B CN 103142819B CN 201310093854 A CN201310093854 A CN 201310093854A CN 103142819 B CN103142819 B CN 103142819B
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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 the preparation method of this Chinese medicine composition simultaneously.
Background technology
Myocardial fibrosis or myocardial hypertrophy be heart long-term load overweight time occur a kind of remodeling ventricle, except connective tissue deposition between myocardial cell, also increase and cell volume increase with cardiac muscle cell protein synthesis, 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 the common complication of valvular heart disease, congenital heart disease, myocardial inflammation etc. and pathologic basis.The myocardial fibrosis continued or myocardial hypertrophy, 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, Endothelin receptor antagonist etc.At present, in these medicines, angiotensin-convertion enzyme inhibitor is only had to achieve certain clinical therapeutic efficacy, but limited use, the effect of obviously resisting myocardial fibrillation or myocardial hypertrophy can not be obtained, other medicines there is no clear evidence display at present can improve myocardial fibrosis or myocardial hypertrophy, so lack with strong points and eutherapeutic medicine at present.Chinese medicine composition involved in the present invention, has determined curative effect, and safety is high, and action target spot enriches, 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 obviously can reduce the heart heavy index, hydroxyproline content, CVF, reduces the fibrous tissue between myocardial cell.
Chinese patent CN102000095A discloses the application of asiaticoside in the medicine preparing prevention or treatment myocardial fibrosis on April 6th, 2011.Asiaticoside has the effect of anti-spontaneous hypertensive rat (SHR) myocardial fibrosis, obviously can reduce heavy, left ventricle weight whole-heartedly, 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 is to have invented myocardial fibrosis or patients with cardiac hypertrophy provides the Chinese medicine composition can preventing and treating 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: Rhizoma Panacis Japonici 15 parts, Fructus Trichosanthis 24 parts, Radix Puerariae 12 parts, Rhizoma Chuanxiong 10 parts, Bulbus Allii Macrostemonis 12 parts.
The above-mentioned Chinese medicine composition of the present invention is the one 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 proves its effect having obvious resisting myocardial fibrillation or myocardial hypertrophy through experiment in vivo.
The present invention gets the ligation of Male Wistar Rats underwent coronary and copies myocardial fibrosis or myocardial hypertrophy animal model, shows the research of above-mentioned Chinese medicine composition:
(1), after myocardial fibrosis or myocardial hypertrophy model group rats give Chinese medicine composition of the present invention, heavy/body weight, ventricle weight/body weight whole-heartedly is obviously reduced.
(2) myocardial fibrosis or myocardial hypertrophy model group rats HE dye and find there is inflammatory cell infiltration widely in heart tissue; Cardiac muscle fiber is ruptured, arrangement disorder; Myocardium cell necrosis.After giving Chinese medicine composition of the present invention, heart tissue inflammatory cell obviously reduces.
(3) myocardial fibrosis or myocardial hypertrophy model group rats Masson dye and find a large amount of collagenic connective tissue hypertrophy.After giving Chinese medicine composition of the present invention, myocardial cell interstitial collagen obviously reduces, and CVF obviously reduces.
Accompanying drawing explanation
Fig. 1 is heart tissue Pathologic changes after HE dyeing, and wherein 1 is pseudo-operation group, and 2 is model group, and 3 is present composition high dose group.
Fig. 2 is heart tissue Pathologic changes after Masson dyeing, and wherein 1 is pseudo-operation group, and 2 is model group, and 3 is present composition high dose group.
Fig. 3 is the change 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.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But concrete material proportion, process conditions and result thereof described by embodiment are only not used in for illustration of the present invention and limit the scope of the 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 equivalence changes and modification fall into the scope of the claims in 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
Resisting myocardial fibrillation or myocardial hypertrophy effect in the body showing Chinese medicine composition of the present invention with experimental data.
1. test medicine
Weighting raw materials 7 staggering amount in proportion, adds 50% alcohol reflux 3 times of 18 times amount, each 1.5 hours respectively.Filter, merge extractive liquid, is evaporated to every milliliter and is equivalent to lg crude drug.
2. laboratory animal
Wiatar rat, male, body weight 250-300g, Shanghai western pul-Bi Kai laboratory animal company limited provides [SCXK (Shanghai) 2008-0016].
3. experimental technique
The foundation of 3.1 myocardial fibrosiies or myocardial hypertrophy model
Be fixed on operating board after rats by intraperitoneal injection 10% chloral hydrate anesthesia (0.3mL100g-1).Open respirator (respiratory frequency 72 min-1, tidal volume 18mL, respiratory quotient is set to 1: 2), insert from rat mouth by tracheal intubation, rise and fall consistent with respirator frequency to rat chest, illustrate and insert trachea.Left front breast unhairing, iodophor disinfection, scalpel cuts skin in the 3rd root bone place, and be separated subcutaneous tissue and muscle along grain of meat, blunt separation the 3rd and the 4th root spatium interosseum, tear pericardium, expose and extrude heart.Suture needle is from pin rat heart left auricle lower edge, and to pulmonary conus, place goes out pin, and depth of needle controls at about 0.1cm, ligation ramus descendens anterior arteriae coronariae sinistrae.Observe left ventricular wall ischemic region cardiac muscle after ligation to bleach, ventricular wall motion weakens, and auricle is obviously congested, namely points out ligation success.Successively close breast after hemostasis, extract endotracheal intubation, cleaning rat airway secretions, puts into cage after it recovers autonomous respiration and be clear-headed.Postoperative every rat muscle injection penicillin 20IU day-1, for three days on end.Pseudo-operation group rat heart arteria coronaria place's threading not ligation, all the other operate same model group.
3.2 grouping administrations
After modeling 2 weeks, animal is divided at random in modeling: myocardial fibrosis or myocardial hypertrophy model group (hereinafter referred to as model group), the large, medium and small dosage group of Chinese medicine composition (12g, 6g, 3g crude drug/kg), positive drug Captopril group (50mg/kg).Add pseudo-operation group and have 6 groups altogether.Every day is administered once, administration volume 10ml/kg, successive administration 4 weeks.Pseudo-operation group and model group give equal-volume distilled water.After modeling the 42nd day, namely after administration the 28th day, last administration post processing animal.
3.3 Indexs measure
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 the outer interstitial collagen over-deposit of fibroblast increased number and myocardial cell.Pivotal role is played in the myocardial fibrosis that TGF-signal beta path causes in various cardiovascular disease.Myocardial hypertrophy is then show as in heart tissue to have inflammatory cell infiltration widely, and cardiac muscle fiber is ruptured, arrangement disorder, myocardium cell necrosis.
The heavy index of the heart: core dirty, weigh, calculate heart/body weight and ventricle/body weight ratio.
Heart tissue hydroxyproline content detects: hydroxyproline is distinctive aminoacid in collagen, and its content can be used for the content analyzing collagen protein in tissue.Take heart and be about 50-100mg, measure hydroxyproline content in heart tissue.
Heart tissue pathological observation: 10% formalin is fixed, 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 sections masson dyes, image is gathered through ZessiAxioskop2 microscope, masson stained positive (collagen in blue) area percentage is calculated through Image-pro plus image processing software analysis, i.e. myocardial collagen fraction by volume (collagen volume fraction, CVF).Often open section random selecting 5 visuals field and do graphical analysis, using CVF average as the measured value of this sample.CVF is larger, represents that collagen content is more.
Heart tissue TGF-β 1 detects: adopt immunohistochemical method to detect the expression of TGF-β 1 in heart tissue.Gather image, often open section random selecting 5 visuals field, gather image, Image-pro plus image processing software automatic analysis calculates positive cell number, using positive cell mean as the measured value of this sample.
4. experimental result
The heavy index of 4.1 hearts: the heart/body weight of model group animal and ventricle/body weight ratio obviously pseudo-operation group high (P < 0.05 ~ 0.01).Compare with model group, Chinese medicine composition of the present invention obviously can reduce heart/body weight and ventricle/body weight value (P < 0.05), has good therapeutical effect to myocardial hypertrophy.In table 1.
Table 1 Chinese medicine composition is on the impact of the heavy coefficient of myocardial fibrosis/rat cardiac hypertrophy heart
Compare with puppet operation group
△ △p < 0.01, compares with model group
*p < 0.05,
*p < 0.01
4.2 heart tissue hydroxyproline contents: model group animal hearts hydroxyproline in tissue and pseudo-operation group obviously increase, after giving Chinese medicine composition of the present invention, in heart tissue, hydroxyproline content obviously reduces (P < 0.05 ~ 0.01).In table 2.
Table 2 Chinese medicine composition is on the impact of 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 heart tissue Pathologic changes
HE stained basis of microscopic observation, pseudo-operation group rat cardiac tissue structural arrangement is neat, has no fracture, degeneration, necrosis and inflammatory cell infiltration; Ventricular endocardium and adventitia no abnormality seen change; Inflammatory cell infiltration is widely had in model group rats heart tissue; Cardiac muscle fiber is ruptured, arrangement disorder; Myocardium cell necrosis.Chinese medicine composition group of the present invention obviously can reduce the lesion degree of animal pattern, reduces the necrosis of inflammatory cell infiltration and myocardial cell.(HE dyes, and sees Fig. 1).
Utilize Masson to dye to rat heart muscle tissue staining, collagen is in blue.Basis of microscopic observation, pseudo-operation group rat heart muscle is organized as redness, has few part collagen in blue; Model group rats cardiac muscular tissue red staining is less, and collagen blue-staining areas is comparatively large, is mainly distributed in myocardial necrosis stove limit (Masson dyes, and sees Fig. 2), shows in the connective tissue proliferation of focus topical collagen, fibrosis occurs.Chinese medicine composition group of the present invention can obviously reduce blue dyeing district, and namely myocardial collagen obviously reduces, and its CVF value comparatively model group obviously reduces (P < 0.05 ~ 0.01).In table 2.
4.4 SABC TGF-β 1 express
Compared with puppet operation group, model group rats cardiac muscular tissue TGF-β 1 expresses remarkable rising, see Fig. 3, TGF-β 1 positive expression cell number significantly raises (p < 0.01), after giving Chinese medicine composition of the present invention, heart tissue TGF-β 1 expresses remarkable reduction (P < 0.01).In table 2.
Above result points out Chinese medicine composition of the present invention to have 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. express at preparation cardiac muscular tissue TGF-β 1 application caused in myocardial fibrosis or myocardial hypertrophy medicine containing the Chinese medicine composition of Rhizoma Panacis Japonici for one kind, it is characterized by described compositions is be 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.
2. according to the application of the Chinese medicine composition described in claim 1, the weight portion that it is characterized by each crude drug in described compositions 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 application of the Chinese medicine composition according to claim 1 or 2, is characterized by described compositions and pharmaceutically acceptable adjuvant, makes tablet, capsule, granule, oral liquid or injection.
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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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| 中药防治心肌肥厚的研究进展;杨冬梅;《2010年中国药学大会暨第十届中国药师周论文集》;20101231;第1-5页 * |
| 现代生物分析法对常用中药的筛选研究;王序等;《北京医科大学学报》;19861231;第18卷(第1期);第31-36页 * |
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