CN102210764B - Application of sweet almond oil in preparing medicament for treating myocardial ischemia reperfusion injury - Google Patents
Application of sweet almond oil in preparing medicament for treating myocardial ischemia reperfusion injury Download PDFInfo
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- CN102210764B CN102210764B CN 201110143641 CN201110143641A CN102210764B CN 102210764 B CN102210764 B CN 102210764B CN 201110143641 CN201110143641 CN 201110143641 CN 201110143641 A CN201110143641 A CN 201110143641A CN 102210764 B CN102210764 B CN 102210764B
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Abstract
The invention provides an application of sweet almond oil in preparing a medicament for treating myocardial ischemia reperfusion injury. The medicament for preventing and treating myocardial ischemia reperfusion injury is prepared from sweet almond oil as an active component and is used in the form of soft capsules which are prepared directly from sweet almond oil by a conventional preparation method of soft capsules. Shown by drug effect tests, the sweet almond oil is capable of improving the hypoxia tolerance of the myocardial tissues of rats, enhancing the tolerance of the myocardial tissues to ischemia reperfusion myocardial injury, improving the antioxidant ability of the myocardial tissues of rats with ischemia reperfusion, and reducing the extent of injury to the myocardial tissues of rats caused by ischemia reperfusion. The almond oil is a natural edible material with unsaturated fatty acid as a main active component, and can not generate toxic side effect on the body when taken in a certain dose range for a long term.
Description
Technical field
The invention belongs to the medicinal preparation technical field of the product that contains raw material or itself and not clear structure, be specifically related to derive from the material of plant.
Background technology
Semen pruni armeniacae oil is to extract a vegetable oil that obtains in the dry fruit of Rosaceae (Rosaceae) cherry Fructus Pruni (Prunus armeniaca L.).Semen pruni armeniacae oil is one of most popular vegetable oil, is faint yellow, and it contains about 90% unsaturated fatty acid, wherein oleic acid 60%, and linoleic acid 30% can reduce the triglyceride in the blood of human body, enhance metabolism, the prevention cardiovascular and cerebrovascular disease is acted on having protected the liver preferably.In addition, Semen pruni armeniacae oil also contains a small amount of needed by human nutrients such as vitamin E, continues to take, and not only is of value to the growth of cerebrovascular and intelligence, also balanced body hormonal system hypophysis cerebri, promotion cell turnover, slow down aging etc. is had special efficacy.Semen pruni armeniacae oil is used for the skin daily nursing, has the magical effect of skin moistening and beauty treatment, therefore is described as by people " natural plants gold ".
Jia Lingyun etc. have inquired into the effect of wild apricot almond oil to hyperlipemia rat liver, the heart, nephridial tissue antioxidant activity; the result shows that wild Prunus armeniaca L.var.ansu Maxim. almond oil has the anti-oxidation protection effect (research of effect of almond oil on hyperlipidemia rats antioxidation to liver, the heart, the kidney of hyperlipemia rat; Northwest Normal University's journal; natural science edition; 2008,4 (2): 92-98).Kong Hao measures almond oil and removes the ability of free radical and calculate corresponding IC50 value by setting up hydroxyl radical free radical, ultra-oxygen anion free radical removing system, the result shows, clearance rate can reach (almond oil and the capability study of Oleum Vitis viniferae removing free radical more than 60% when almond oil concentration is 0.1mg/mL, gansu science and technology, 2008,24 (6): 57-58).Wang Jianhuas etc. are by being divided into 200 routine patients of cervical ruin at random treatment group 108 examples (with almond oil cotton balls vagina administration) and matched group 92 examples (using the interferon suppository vagina administration), 2 groups all treat 3 courses for the treatment of after, find that almond oil has the (clinical research of almond oil treatment cervical erosion of certain curative effect to cervical erosion, the Jiangxi Chinese medicine, 2006 (6): 32).The west of a river, the Tianjin Wang Wei of hospital has obtained promising result (skilful use almond oil treatment " yellow fluid bubble ", Tianjin nursing, 1996,12 (4): 167-168) with almond oil treatment " yellow fluid bubble " clinical observation 10 examples.Report is arranged, and almond oil has significant protective effect to carbon tetrachloride hepatic injury, and (FoodChem 2011; 125:673-678).
Cardiovascular disease has become the first killer of harm humans health, along with the raising of people's living standard, the quickening of rhythm of life, the increasing of job and life stress, the sickness rate of cardiovascular disease, mortality rate are obvious ascendant trend, the serious harm mankind's life quality.Myocardial ischemia reperfusion injury refers to cause a kind of pathological process of again recovering blood supply behind the myocardial ischemia because of blood supply disorder.The key of myocardial damage treatment is to alleviate the damage after the myocardium severe ischemic anoxia or strengthens myocardial cell to the resistivity of hypoxic-ischemic damage.The medicine that is usually used in myocardial ischemia reperfusion injury can be divided into five classes: (1) anticoagulation medicine, such as aspirin, warfarin; (2) coronary artery dilator class medicine is such as nitric acid lipid, calcium ion antagonist; (3) beta-blocker is such as atenolol, metoprolol; (4) adrenergic blocking agent is such as metoprolol; (5) digitalis is such as digoxin etc.; (6) other also has antihypertensive drug and regulates blood glucose, blood-lipoids medicine, such as statins.But the use of these medicines all can produce certain side effect to health to a certain extent.
Summary of the invention
The present invention after alleviating myocardium severe ischemic anoxia damage or strengthen myocardial cell to the resistivity of hypoxic-ischemic damage, overcome the shortcoming of above-mentioned treatment medicament for myocardial ischemia-reperfusion injury, for Semen pruni armeniacae oil provides a kind of new purposes.
Solving the problems of the technologies described above the technical scheme that adopts is: the purposes of Semen pruni armeniacae oil in preparation treatment medicament for myocardial ischemia-reperfusion injury.
The purposes of Semen pruni armeniacae oil in preparation myocardial damage protection medicine.
Semen pruni armeniacae oil is purchased from the natural articles for use company limited in green fragrant island, Guangzhou.Medicine with Semen pruni armeniacae oil preparation treatment myocardial ischemia reperfusion injury uses Semen pruni armeniacae oil with the form of soft capsule, described soft capsule is made according to the preparation technology of soft capsule routine, every heavy 0.8g of soft capsule.
Semen pruni armeniacae oil is with the usage and dosage of soft capsule: become human oral, each 12 of prevention myocardial damage dosage, every day 1 time, each 12 for the treatment of myocardial ischemia reperfusion injury dosage, every day 2 times.
Medicine of the present invention shows through the test of pesticide effectiveness; Semen pruni armeniacae oil has obvious protective effect to the Ischemia Reperfusion rat myocardium from injury; can improve the hypoxia-bearing capability of rat heart muscle tissue; strengthen cardiac muscular tissue to the tolerance of Ischemia Reperfusion myocardial damage; improve the oxidation resistance of Ischemia Reperfusion rat heart muscle tissue, reduce Ischemia Reperfusion to the degree of injury of rat heart muscle tissue.Almond oil is the natural edible material take unsaturated fatty acid as main effective ingredient, and in certain amount ranges, long-term taking can not cause toxic and side effects to health.
The specific embodiment
The present invention is described in more detail below in conjunction with embodiment, but the invention is not restricted to these embodiment.
Embodiment 1
Do not add any adjuvant take 1000 of production soft capsule products of the present invention as example, directly the 800g Semen pruni armeniacae oil is made soft capsule, every heavy 0.8g according to the conventional preparation technology of soft capsule.
Usage and dosage: become human oral, each 12 of preventive dose, every day 1 time, each 12 of therapeutic dose, every day 2 times.
In order to verify the beneficial effect of effective ingredient Semen pruni armeniacae oil treatment myocardial ischemia-reperfusion damage, the inventor has carried out the test of pesticide effectiveness with Semen pruni armeniacae oil, and concrete test situation is as follows:
Tested medicine: Semen pruni armeniacae oil is purchased from the natural articles for use company limited in green fragrant island, Guangzhou.
Experiment material: nitricoxide synthase (NOS), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), nitric oxide and malonaldehyde (MDA) testing cassete build up bio-engineering research by Nanjing to be provided.
Experimental apparatus: DF-101S heat collecting type constant-temperature heating magnetic stirring apparatus, produced by Zhengzhou Greatwall Scientific Industrial ﹠ Trading Co., Ltd.; HR-120 type precise electronic balance is produced by Japan; The BI-90Plus laser particle analyzer is produced by German Brooker Hai Wen instrument company; The TU-1810 ultraviolet-uisible spectrophotometer is produced by the Beijing Puxi General Instrument Co., Ltd; High speed low temperature centrifugal machine UNIVERSAL320R, Hettich-zentrifugen is produced by Germany.
Animal subject: healthy male SD rat, body weight 200～220g is provided by Xi'an Jiaotong University Medical College's Experimental Animal Center, and the animal quality certification moves word 08-005 number for the doctor; The rat solid feed is provided by Xi'an Jiaotong University Medical College's Experimental Animal Center, all experimental animal feeding term harmonizations.
1, laboratory animal and grouping
Healthy male SD rat is divided into sham operated rats, Ischemia Reperfusion group at random, dosage group, Semen pruni armeniacae oil high dose group in Semen pruni armeniacae oil low dose group, the Semen pruni armeniacae oil, every group each 12, adaptability is raised after 7 days and is tested.Before the Ischemia Reperfusion, the tap water of sham operated rats and Ischemia Reperfusion group gavage every day 6mL/kg body weight, the Semen pruni armeniacae oil of dosage group, Semen pruni armeniacae oil high dose group difference every day gavage 2mL/kg, 6mL/kg, 10mL/kg body weight in Semen pruni armeniacae oil low dose group, the Semen pruni armeniacae oil, gavage is 14 days continuously.
2, model preparation
The 15th day with mass fraction be 5% pentobarbital sodium water solution by 30mg/kg body weight intraperitoneal anesthesia rat, dorsal position is fixed, and connects the toy respirator, opens breast in third and fourth intercostal space of left border of sternum and exposes heart, keeps pleura complete.Be followed between pulmonary conus and left auricle and find out left anterior descending coronary artery, and place 2mm place ligation under the ramus descendens anterior arteriae coronariae sinistrae initial part, only not ligation of threading of sham operated rats with circular noinvasive sewing needle 4/0 silk thread sub-thread.With ECG T wave toweringly merge with the QRS ripple, the QRS ripple amplitude that broadens adds the greatly sign of ligation success.Ligation is unclamped ligature and was poured into 120 minutes again after 30 minutes.
3, detect index and method
Pour into again and got blood by coeliac artery in 120 minutes, preparation serum, the activity of mensuration serum creatine kinase (CK) and glutamic oxaloacetic transaminase, GOT (AST).Get the complete heart of winning rapidly of blood, part is cleaned blood input liquid nitrogen with the ice normal saline and is saved backup, measure nitricoxide synthase (NOS), superoxide dismutase (SOD), catalase (CAT), the activity of glutathion peroxidase (GSH-Px) and the content of nitric oxide (NO) and malonaldehyde (MDA), measurement result sees Table 1～4.The heart that part is won turns white from aortic arch cannula and with normal saline flushing to heart immediately, be that 5% chloro triphenyltetrazolium chloride (TTC) aqueous solution pours into to heart and reddens with mass fraction again, drop into immediately liquid nitrogen, taking out section after 20 minutes, to put mass fraction into be to fix 12 hours in 10% the formalin, the infarction position is pale asphyxia, and other positions are red, takes pictures to blot with filter paper afterwards, separate the infarction position and weigh, calculate infarction and gross weight ratio.
Result of calculation sees Table 1.
4, statistical procedures
Each is organized data and represents with mean+SD, adopts the t-test and judge respectively to organize the significance degree of difference, uses the statistic software SPSS deal with data.
5, experimental result and analysis
(1) Semen pruni armeniacae oil is on the impact of activity of serum enzyme and myocardial infarction degree
By as seen from Table 1, Ischemia Reperfusion group serum CK and AST activity are apparently higher than sham operated rats (p＜0.05), and the rising amplitude is respectively 23.81% and 22.61%; The rat blood serum enzymatic activity of respectively organizing of taking Semen pruni armeniacae oil obviously reduces; significant difference (p＜0.05) is all arranged; along with the increase rat blood serum enzymatic activity of gavage dosage has descended respectively 7.69%, 35.90%, 82.05%, illustrate that damage may have certain protective effect to Semen pruni armeniacae oil to myocardial ischemia-reperfusion.
The TTC coloration result shows, sham operated rats, the Ischemia Reperfusion group, the Semen pruni armeniacae oil low dose group, dosage group in the Semen pruni armeniacae oil, Semen pruni armeniacae oil high dose group rat myocardium from injury or infarction weight rate are respectively 5.14%, 20.41%, 19.65%, 14.60%, 7.35%, Ischemia Reperfusion group weight ratio almost is 4 times of sham operated rats, taking each rising infarction weight ratio of organizing along with gavage dosage of Semen pruni armeniacae oil reduces gradually, low dose group is compared with sham operated rats does not have significant difference (P＞0.05), the high dose group effect is the most obvious, has reduced nearly 3 times than Ischemia Reperfusion group.This experiment has further confirmed the protective effect of Semen pruni armeniacae oil to the myocardial ischemia-reperfusion damage.
Table 1 is respectively organized rat blood serum enzymatic activity and myocardial infarction weight rate
| Group | CK active (U/ml) | AST active (U/ml) | Infarction weight rate (%) |
| Sham operated rats | 0.63±0.08 | 44.68±3.94 | 5.14±0.37 |
| The Ischemia Reperfusion group | 0.78±0.10 ▲ | 54.78±2.40 ▲ | 20.41±1.04 ▲ |
| The Semen pruni armeniacae oil low dose group | 0.72±0.04 ▲ | 39.14±3.75 ★ | 19.65±0.60 ▲ |
| Dosage group in the Semen pruni armeniacae oil | 0.50±0.06 ▲★# | 39.86±2.43 ★ | 14.60±0.62 ▲★# |
| The Semen pruni armeniacae oil high dose group | 0.14±0.02 ▲#★＊ | 40.79±4.22 ★ | 7.35±0.43 ▲★#＊ |
In the table ▲ represent with sham operated rats significant difference (P＜0.05) is arranged; ★ represents with the Ischemia Reperfusion group significant difference (P＜0.05) is arranged; # represents with the Semen pruni armeniacae oil low dose group significant difference (P＜0.05) is arranged; * the dosage group has significant difference (P＜0.05) in expression and the Semen pruni armeniacae oil.
(2) Semen pruni armeniacae oil is on the impact of myocardium CK and AST enzymatic activity
Table 2 is respectively organized rat heart muscle CK and AST enzymatic activity
In the table ▲ represent with sham operated rats significant difference (P＜0.05) is arranged; ★ represents with the Ischemia Reperfusion group significant difference (P＜0.05) is arranged.
By as seen from Table 2, CK and AST enzymatic activity are all in rising trend in the Ischemia Reperfusion rear myocardium tissue, ascensional range be respectively 6.24% and 13.68%, AST enzymatic activity change to compare with sham operated rats and have significant difference (P＜0.05).The active reason that raises of CK may be a kind of biological compensatory response that cardiac muscular tissue occurs in order to obtain more adenosine triphosphate under ischemia/anaerobic condition.In addition, under ischemia/anaerobic condition, aerobic metabolism is obstructed, cardiac muscular tissue also can obtain more adenosine triphosphate by glycolytic pathway, cause the accumulation of aerobic metabolism intermediate product α-ketoglutaric acid, α-ketoglutaric acid activates AST as the substrate of the transamination reaction of AST catalysis, raises so that AST is active.The experiment of having taken Semen pruni armeniacae oil organizes respectively that rat heart muscle is organized CK and AST is active obviously descends, and comparing with the Ischemia Reperfusion group all has significant difference (P＜0.05), but does not have obvious dose relationship.Illustrate that Semen pruni armeniacae oil can improve the hypoxia-bearing capability of rat heart muscle tissue, strengthen cardiac muscular tissue to the tolerance of Ischemia Reperfusion myocardial damage.
(3) Semen pruni armeniacae oil is on the impact of myocardium activities of antioxidant enzymes and MDA content
Table 3 is respectively organized rat heart muscle SOD, CAT, GSH-Px enzymatic activity and MDA content
In the table ▲ represent with sham operated rats significant difference (P＜0.05) is arranged; ★ represents with the Ischemia Reperfusion group significant difference (P＜0.05) is arranged.
By as seen from Table 3, SOD, CAT and GSH-Px activity all have decline in various degree behind Ischemia Reperfusion, MDA content slightly has rising, SOD compares with sham operated rats with the GSH-Px activity change has significant difference (P＜0.05), and CAT is active to compare there was no significant difference (P＞0.05) with the MDA changes of contents with sham operated rats.After taking Semen pruni armeniacae oil, several activities of antioxidant enzymes all have rising in various degree in the rat heart muscle tissue, but all do not present obvious dose-effect relationship.Wherein the SOD activity change of Semen pruni armeniacae oil Three doses group is compared with the Ischemia Reperfusion group all has significant difference (P＜0.05), low, the middle dosage group of Semen pruni armeniacae oil GSH-Px activity change is compared with the Ischemia Reperfusion group all has significant difference (P＜0.05), Semen pruni armeniacae oil Three doses group CAT activity change is the most obvious, and comparing with the Ischemia Reperfusion group with sham operated rats all has significant difference (P＜0.05).Result of the test shows, Semen pruni armeniacae oil can improve the oxidation resistance of Ischemia Reperfusion rat heart muscle tissue, reduces Ischemia Reperfusion to the degree of injury of rat heart muscle tissue.
(4) Semen pruni armeniacae oil is on the impact of myocardium NOS activity and NO content
Table 4 is respectively organized rat NOS activity and NO content
In the table ▲ represent with sham operated rats significant difference (P＜0.05) is arranged; ★ represents with the Ischemia Reperfusion group significant difference (P＜0.05) is arranged.
By as seen from Table 4, cNOS is active in the Ischemia Reperfusion rear myocardium tissue descends, and iNOS is active to rise, but with sham operated rats there was no significant difference (P＞0.05), NO content significantly reduces (P＜0.05); Active obviously rise (P＜0.05) of the cNOS of Semen pruni armeniacae oil Three doses group, the iNOS activity is on a declining curve, Semen pruni armeniacae oil low dose group and high dose group and Ischemia Reperfusion group have significant difference (P＜0.05), and each group of NO content all has significance rising (P＜0.05)., the result of the test explanation, Semen pruni armeniacae oil is relevant with the blood vessel dilating effect of NO to the protective effect of the myocardial damage of Ischemia Reperfusion rat.
6, conclusion (of pressure testing)
Semen pruni armeniacae oil has obvious protection and therapeutical effect to the Ischemia Reperfusion rat myocardium from injury; it can improve the hypoxia-bearing capability of rat heart muscle tissue; strengthen cardiac muscular tissue to the tolerance of Ischemia Reperfusion myocardial damage; improve the oxidation resistance of Ischemia Reperfusion rat heart muscle tissue, reduce Ischemia Reperfusion to the degree of injury of rat heart muscle tissue.
Claims (1)
1. Semen pruni armeniacae oil is preparing the purposes for the treatment of in the medicament for myocardial ischemia-reperfusion injury.
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