CN102210764B - Application of sweet almond oil in preparing medicament for treating myocardial ischemia reperfusion injury - Google Patents

Abstract

A sweet almond oil is used in the preparation of a medicine for treating myocardial ischemia-reperfusion injury. The sweet almond oil is used as an active ingredient to prepare the medicine for preventing and treating myocardial ischemia-reperfusion injury and is used in the form of soft capsules. The soft capsules are directly used in sweetened Almond oil adopts the preparation method of conventional soft capsule to make. Sweet almond oil has undergone drug efficacy tests, showing that sweet almond oil can improve the hypoxia resistance of rat myocardial tissue, enhance the tolerance of myocardial tissue to ischemia-reperfusion myocardial injury, and improve the ischemia-reperfusion rat myocardial tissue. Antioxidant ability, reduce ischemia-reperfusion damage to myocardial tissue in rats. The almond oil of the present invention is a natural edible substance with unsaturated fatty acid as the main active ingredient, and within a certain dosage range, long-term use will not cause toxic and side effects to the body.

Description

Application of sweet almond oil in preparation of medicine for treating myocardial ischemia-reperfusion injury

technical field

The invention belongs to the technical field of medical preparations containing raw materials or their reaction products with unknown structures, and specifically relates to materials derived from plants.

Background technique

Sweet almond oil is a vegetable oil extracted from the dried fruit of Prunus armeniaca L. in the family Rosaceae. Sweet almond oil is one of the most widely used vegetable oils. It is light yellow in color. It contains about 90% unsaturated fatty acids, including 60% oleic acid and 30% linoleic acid. It can reduce triglycerides in human blood and promote metabolism. , has a better effect on preventing cardiovascular and cerebrovascular diseases and protecting the liver. In addition, sweet almond oil also contains a small amount of vitamin E and other essential nutrients for the human body. Continuous consumption is not only beneficial to the development of cerebrovascular and intelligence, but also has special effects on balancing the pituitary gland in the endocrine system, promoting cell renewal, and delaying aging. Sweet almond oil is used in daily skin care and has magical effects of moisturizing and beautifying, so it is known as "natural plant gold".

Jia Lingyun et al. explored the effect of wild almond oil on the liver, heart and kidney tissue antioxidant activity of hyperlipidemia rats, and the results showed that wild almond oil had antioxidant protective effect on the liver, heart and kidney of hyperlipidemia rats ( Research on the antioxidant effect of almond oil on rats with experimental hyperlipidemia, Journal of Northwest Normal University, Natural Science Edition, 2008, 4(2):92-98). Kong Hao measured the ability of almond oil to scavenge free radicals by establishing a hydroxyl radical and superoxide anion radical scavenging system and calculated the corresponding IC50 value. The results showed that when the concentration of almond oil was 0.1mg/mL, the scavenging rate could reach 60%. The above (Research on the ability of almond oil and grape seed oil to scavenge free radicals, Gansu Science and Technology, 2008, 24(6): 57-58). Wang Jianhua et al. randomly divided 200 patients with cervical erosion into a treatment group of 108 cases (administered vaginally with almond oil cotton balls) and a control group of 92 cases (administered vaginally with interferon suppositories). Both groups were treated for 3 courses. It was found that almond oil has a certain curative effect on cervical erosion (Clinical research on the treatment of cervical erosion with almond oil, Jiangxi Traditional Chinese Medicine, 2006 (6): 32). Wang Wei of Tianjin Hexi Hospital used almond oil to treat "yellow blisters" in clinical observation of 10 cases, and achieved satisfactory results (Skillfully using almond oil to treat "yellow blisters", Tianjin Nursing, 1996, 12(4): 167-168). It has been reported that almond oil has a significant protective effect on carbon tetrachloride liver injury (FoodChem 2011; 125: 673-678).

Cardiovascular disease has become the number one killer that endangers human health. With the improvement of people's living standards, the acceleration of the pace of life, and the increase in the pressure of work and life, the incidence and mortality of cardiovascular diseases are on the rise, seriously endangering human beings. quality of life. Myocardial ischemia-reperfusion injury refers to a pathological process in which blood supply is restored after myocardial ischemia caused by blood supply disturbance. The key to the treatment of myocardial injury is to reduce myocardial damage after severe ischemia and hypoxia or to enhance the resistance of myocardial cells to ischemia and hypoxia injury. Drugs commonly used for myocardial ischemia-reperfusion injury can be divided into five categories: (1) anticoagulant drugs, such as aspirin and warfarin; (2) coronary artery dilating drugs, such as nitrates and calcium ion antagonists; (3) β-receptor blockers, such as propranolol and metoprolol; (4) adrenergic blockers, such as betoprolol; (5) digitalis, such as digoxin, etc.; (6) Others include antihypertensive drugs and drugs for regulating blood sugar and blood lipids, such as statins. However, the use of these drugs will have certain side effects on the body to a certain extent.

Contents of the invention

The present invention starts from reducing the damage of myocardial severe ischemia and hypoxia or enhancing the resistance of myocardial cells to ischemia and hypoxia damage, overcomes the shortcomings of the above-mentioned medicine for treating myocardial ischemia-reperfusion injury, and provides a new application for sweet almond oil .

The technical scheme adopted for solving the above-mentioned technical problems is: the application of sweet almond oil in the preparation of medicine for treating myocardial ischemia-reperfusion injury.

Use of sweet almond oil in the preparation of myocardial injury protection medicine.

Sweet almond oil was purchased from Guangzhou Lvxiangdao Natural Products Co., Ltd. Sweet almond oil is used to prepare the medicine for treating myocardial ischemia-reperfusion injury, and the sweet almond oil is used in the form of soft capsules. The soft capsules are made according to the conventional preparation process of soft capsules. Each soft capsule Weighs 0.8g.

Dosage of sweet almond oil in soft capsules: Oral for adults, 12 capsules each time for the prevention of myocardial injury, once a day, 12 capsules each time for the treatment of myocardial ischemia-reperfusion injury, 2 times a day.

Drug efficacy tests of the present invention show that sweet almond oil has obvious protective effect on myocardial injury of ischemia-reperfusion rats, can improve the hypoxia resistance of rat myocardial tissue, and enhance the ability of myocardial tissue to ischemia-reperfusion myocardial injury. Tolerance ability, improve the antioxidant capacity of ischemia-reperfusion rat myocardial tissue, and reduce the damage degree of ischemia-reperfusion rat myocardial tissue. Almond oil is a natural edible substance with unsaturated fatty acid as the main active ingredient. Within a certain dosage range, long-term use will not cause toxic and side effects to the body.

Detailed ways

The present invention will be described in further detail below in conjunction with the examples, but the present invention is not limited to these examples.

Example 1

Taking the production of 1000 soft capsule products of the present invention as an example, without adding any auxiliary materials, 800g sweet almond oil is directly made into soft capsules according to the conventional preparation process of soft capsules, and every grain weighs 0.8g.

Usage and dosage: Oral for adults, preventive dosage is 12 capsules each time, once a day, and therapeutic dosage is 12 capsules each time, twice a day.

In order to verify the beneficial effect of active ingredient sweet almond oil in treating myocardial ischemia-reperfusion injury, the inventor has carried out a drug effect test with sweet almond oil, and the specific test conditions are as follows:

Test drug: sweet almond oil, purchased from Guangzhou Lvxiangdao Natural Products Co., Ltd.

Experimental materials: nitric oxide synthase (NOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), nitric oxide and malondialdehyde The (MDA) test box was provided by Nanjing Jiancheng Bioengineering Institute.

Experimental instruments: DF-101S collector type constant temperature heating magnetic stirrer, produced by Zhengzhou Great Wall Technology Industry and Trade Co., Ltd.; HR-120 precision electronic balance, produced in Japan; BI-90Plus laser particle size analyzer, produced by Germany Brookhaven Instruments Produced by the company; TU-1810 ultraviolet-visible spectrophotometer, produced by Beijing Puxi General Instrument Co., Ltd.; high-speed low-temperature centrifuge UNIVERSAL320R, Hettich-zentrifugen, produced in Germany.

Test animals: healthy male SD rats, weighing 200-220g, provided by the Experimental Animal Center of Xi'an Jiaotong University School of Medicine, the animal qualification certificate is Yidongzi No. 08-005; Provided by the Experimental Animal Center, all experimental animals were kept under the same conditions.

1. Experimental animals and grouping

Healthy male SD rats were randomly divided into sham operation group, ischemia-reperfusion group, sweet almond oil low-dose group, sweet almond oil middle-dose group, and sweet almond oil high-dose group, with 12 rats in each group and adaptive feeding for 7 days. The experiment was carried out a few days later. Before ischemia-reperfusion, the sham operation group and the ischemia-reperfusion group were intragastrically administered 6 mL/kg body weight of tap water every day, and the sweet almond oil low-dose group, sweet almond oil middle-dose group, and sweet almond oil high-dose group were intragastrically administered 2 mL per day. /kg, 6mL/kg, 10mL/kg body weight of sweet almond oil, continuous gavage for 14 days.

2. Model preparation

On the 15th day, rats were intraperitoneally anesthetized with 5% pentobarbital sodium aqueous solution at 30 mg/kg body weight, fixed in the supine position, connected to a small animal ventilator, and exposed the heart by opening the third and fourth intercostal spaces at the left sternal border , keep the pleura intact. Then find the left anterior descending coronary artery between the conus pulmonary artery and the left atrial appendage, and place a single strand of 4/0 silk thread with a round non-invasive suture needle at 2 mm below the initial part of the left anterior descending coronary artery for ligation. ligation. The fusion of towering T wave and QRS wave in electrocardiogram, and the widening and amplitude of QRS wave are the signs of successful ligation. After 30 minutes of ligation, loosen the ligature and reperfuse for 120 minutes.

3. Detection indicators and methods

After 120 minutes of reperfusion, blood was collected through the celiac artery, serum was prepared, and the activities of serum creatine kinase (CK) and aspartate aminotransferase (AST) were measured. After blood collection, the heart was quickly removed, some of the blood was washed with ice saline and stored in liquid nitrogen for later use, and the nitric oxide synthase (NOS), superoxide dismutase (SOD), catalase (CAT), glutamate The activity of glutathione peroxidase (GSH-Px) and the contents of nitric oxide (NO) and malondialdehyde (MDA) are shown in Tables 1-4. The partially removed heart was immediately intubated from the aortic arch and flushed with normal saline until the heart turned pale, then perfused with 5% triphenyltetrazolium chloride (TTC) aqueous solution until the heart turned red, and immediately put into liquid nitrogen. After 20 minutes, take out the slices and put them in 10% formaldehyde solution for 12 hours. The infarction part is pale and the other parts are red. After taking pictures, dry them with filter paper, separate the infarction parts and weigh them, and calculate the ratio of infarction to total weight. .

The calculation results are shown in Table 1.

4. Statistical processing

The data of each group were expressed as mean ± standard deviation, and the t-test was used to judge the significance of the differences among the groups, and the statistical software SPSS was used to process the data.

5. Experimental results and analysis

(1) Effect of sweet almond oil on serum enzyme activity and degree of myocardial infarction

As can be seen from Table 1, the serum CK and AST activities of the ischemia-reperfusion group were significantly higher than those of the sham operation group (p<0.05), and the increase range was 23.81% and 22.61% respectively; Significant difference is all arranged (p＜0.05), and along with the increase of intragastric administration dose, rat serum enzyme activity has decreased respectively 7.69%, 35.90%, 82.05%, illustrates that sweet almond oil may be to myocardial ischemia-reperfusion injury. Has a certain protective effect.

The results of TTC staining showed that the weight ratios of myocardial injury or infarction in rats in the sham operation group, ischemia-reperfusion group, sweet almond oil low dose group, sweet almond oil medium dose group, and sweet almond oil high dose group were 5.14% and 20.41%, respectively. , 19.65%, 14.60%, 7.35%, the weight ratio of the ischemia-reperfusion group was almost 4 times that of the sham operation group, and the infarction weight ratio of the groups taking sweet almond oil gradually decreased with the increase of the intragastric administration dose, and the low-dose group and the Compared with the sham operation group, there was no significant difference (P>0.05), and the effect of the high-dose group was the most obvious, which was nearly 3 times lower than that of the ischemia-reperfusion group. This experiment further confirmed the protective effect of sweet almond oil on myocardial ischemia-reperfusion injury.

Table 1 Rats of serum enzyme activity and myocardial infarction weight ratio in each group

group CK activity (U/ml) AST activity (U/ml) Infarct weight ratio (%) mock surgical group 0.63±0.08 44.68±3.94 5.14±0.37 Ischemia-reperfusion group 0.78±0.10 ^▲ 54.78±2.40 ^▲ 20.41±1.04 ^▲ Sweet almond oil low dose group 0.72±0.04 ^▲ 39.14±3.75 ^★ 19.65±0.60 ^▲ Medium dose group of sweet almond oil 0.50±0.06 ^▲★# 39.86±2.43 ^★ 14.60±0.62 ^▲★# Sweet almond oil high dose group 0.14±0.02 ^▲#★＊ 40.79±4.22 ^★ 7.35±0.43 ^▲★#＊

In the table, ▲ indicates that there is a significant difference with the sham operation group (P<0.05); ★ indicates that there is a significant difference with the ischemia-reperfusion group (P＜0.05); # indicates that there is a significant difference with the sweet almond oil low-dose group ( P<0.05); * indicates that there is a significant difference (P<0.05) from the sweet almond oil middle dose group.

(2) Effect of sweet almond oil on myocardial CK and AST enzyme activity

Table 2 Myocardial CK and AST enzyme activities of rats in each group

In the table, ▲ indicates a significant difference with the sham operation group (P<0.05); ★ indicates a significant difference with the ischemia-reperfusion group (P<0.05).

It can be seen from Table 2 that after ischemia-reperfusion, the enzyme activities of CK and AST in the myocardial tissue showed an upward trend, and the increase rate was 6.24% and 13.68%, respectively, and the change of AST enzyme activity was significantly different from that of the sham group (P< 0.05). The reason for the increase of CK activity may be a kind of biological compensatory reaction for myocardial tissue to obtain more adenosine triphosphate under ischemia/hypoxia state. In addition, in the state of ischemia/hypoxia, aerobic metabolism is blocked, and myocardial tissue will obtain more adenosine triphosphate through glycolysis, resulting in the accumulation of α-ketoglutarate, an intermediate product of aerobic metabolism, α-ketoglutarate Diacids act as substrates for AST-catalyzed transamination reactions to activate AST, leading to increased AST activity. The activities of CK and AST in the myocardial tissue of the rats in the experimental groups that took sweet almond oil decreased significantly, compared with the ischemia-reperfusion group (P<0.05), but there was no obvious dose relationship. It shows that sweet almond oil can improve the hypoxia tolerance of rat myocardial tissue, and enhance the tolerance of myocardial tissue to ischemia-reperfusion myocardial injury.

(3) Effect of sweet almond oil on myocardial antioxidant enzyme activity and MDA content

Table 3 Myocardial SOD, CAT, GSH-Px enzyme activity and MDA content of rats in each group

In the table, ▲ indicates a significant difference with the sham operation group (P<0.05); ★ indicates a significant difference with the ischemia-reperfusion group (P<0.05).

It can be seen from Table 3 that the activities of SOD, CAT and GSH-Px all decreased to varying degrees after ischemia-reperfusion, and the content of MDA increased slightly. P<0.05), CAT activity and MDA content changes compared with the sham operation group had no significant difference (P>0.05). After taking sweet almond oil, the activities of several antioxidant enzymes in myocardial tissue of rats all increased to varying degrees, but none of them showed a significant dose-effect relationship. Among them, the SOD activity changes of the three dose groups of sweet almond oil were significantly different from those of the ischemia-reperfusion group (P<0.05). There were significant differences (P<0.05) compared with all the three doses of sweet almond oil groups, and the CAT activity changes were the most obvious, compared with the sham operation group and the ischemia-reperfusion group (P<0.05). The test results show that sweet almond oil can improve the antioxidant capacity of myocardial tissue of rats with ischemia-reperfusion, and reduce the degree of injury of myocardial tissue of rats with ischemia-reperfusion.

(4) Effect of sweet almond oil on myocardial NOS activity and NO content

Table 4 NOS activity and NO content of rats in each group

In the table, ▲ indicates a significant difference with the sham operation group (P<0.05); ★ indicates a significant difference with the ischemia-reperfusion group (P<0.05).

It can be seen from Table 4 that after ischemia-reperfusion, the cNOS activity in the myocardial tissue decreased, and the iNOS activity increased, but there was no significant difference with the sham operation group (P>0.05), and the NO content decreased significantly (P<0.05); sweet almond oil three The cNOS activity in the three dose groups increased significantly (P<0.05), and the iNOS activity showed a downward trend. There was a significant difference between the sweet almond oil low-dose group and high-dose group and the ischemia-reperfusion group (P<0.05), and the NO content in each group All were significantly increased (P<0.05). , the test results show that the protective effect of sweet almond oil on myocardial injury in rats with ischemia-reperfusion is related to the dilating effect of NO on blood vessels.

6. Test conclusion

Sweet almond oil has obvious protective and therapeutic effects on myocardial injury of ischemia-reperfusion rats, which can improve the hypoxia tolerance of rat myocardial tissue, enhance the tolerance of myocardial tissue to ischemia-reperfusion myocardial injury, and improve the Anti-oxidation ability of myocardial tissue of rats with blood reperfusion, and reduce the degree of injury of ischemia-reperfusion to myocardial tissue of rats.

Claims (1)

1. the purposes of sweet almond oil in the preparation treatment myocardial ischemia-reperfusion injury medicine.