CN107496390B - Application of hematoxylin A derivative in protecting heart damage caused by chemotherapeutic drugs - Google Patents
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Abstract
The invention discloses application of a hematoxylin A derivative in protecting heart damage caused by chemotherapeutic drugs. The chemical structural formula of the protosappanin A derivative is shown as a general formula I. The invention researches the function and mechanism of the protosappanin A derivative for protecting the heart damage induced by chemotherapy drug adriamycin, and the research result shows that the protosappanin A derivative can relieve the myocardial damage induced by adriamycin and the myocardial apoptosis and oxidative stress damage, thereby being capable of being used as a heart protection drug. The present invention provides a new and effective therapeutic approach for treating or preventing cardiac damage caused by chemotherapy drug treatment.
Description
Technical Field
The invention relates to a new application of a protosappanin A derivative, in particular to an application of the protosappanin A derivative in protecting heart damage caused by chemotherapy drugs. The invention belongs to the technical field of medicines.
Background
At present, the incidence of tumors is higher and higher, the quality of life of people is greatly reduced, but with the continuous improvement of medical technology research and the wide application of anti-tumor drugs, the survival time of tumor patients is remarkably prolonged, some tumors can directly affect cardiac vessels and accessory structures thereof to cause serious harm, and the potential cardiovascular damage and cardiovascular system diseases of tumor treatment become health problems which cannot be ignored for the tumor patients.
There are 4 common chemotherapeutic drugs that can cause different cardiovascular damage: cyclophosphamide belongs to alkylating agents, and can induce the occurrence of heart diseases such as nonspecific T wave or ST segment abnormality and tachyarrhythmia; paclitaxel, which can act on microtubule cells to achieve anti-tumor effect, but is easy to induce bradycardia, myocarditis, etc.; the antimetabolite fluorouracil can cause angina; the anthracycline doxorubicin induces different diseases at different times after administration, transient arrhythmia within hours after administration, congestive heart failure within one year of administration, and the like.
The anthracycline doxorubicin is the most commonly used chemotherapeutic drug, has recognized the anti-tumor effect, and is used for treating various malignant tumors clinically. However, adriamycin has obvious toxic and side effects on the heart and is dose-dependent, and congestive heart failure is easy to occur if the administration time reaches the last year, and the death rate of the adriamycin can reach 30-50 percent, so the clinical application of the adriamycin is strictly controlled. The mechanism of action of doxorubicin on cardiotoxicity is not clear, but it is considered that it is one of the problems in tumor therapy because a large amount of superoxide radicals and lipid peroxidation are formed, and the compounds such as enzymes related to energy metabolism of cardiac muscle cells are changed, so that metabolic disorders, and finally, cardiac muscle cell necrosis and apoptosis are caused, and more cardiac function damage is caused than the early occurrence of drug administration.
Dexrazoxane developed in the united states today is shown to have a myocardial protective effect in patients treated with tumor chemotherapy, the mechanism of which is mainly that the drug inhibits the binding of iron ions to doxorubicin by binding with iron ions, thereby reducing superoxide radical formation, and inhibiting oxidative stress level to alleviate cardiomyocyte degeneration and necrosis, but it is easily tolerated and reduces the anti-tumor effect of doxorubicin while alleviating cardiotoxicity. Therefore, the search for a new protective agent for protecting the cardiotoxicity caused by chemotherapeutic drugs without reducing the antitumor effect of the chemotherapeutic drugs becomes an urgent need for the clinical application of chemotherapeutic drugs.
The development of traditional Chinese medicines and the finding of new heart protection medicines, in particular to protection medicines for heart damage caused by chemotherapy medicines, have Chinese characteristics, accord with Chinese situations, and are a chance to push traditional Chinese medicines to the world. The traditional Chinese medicine has rich resources, high availability, small side effect, few toxic and side effects and low price. Therefore, the traditional Chinese medicine or the effective components with the heart protection effect are searched, the action mechanism of the traditional Chinese medicine or the effective components is deeply researched, the pain and the economic burden of patients can be relieved, more patients can receive chemotherapy, the life of the patients is prolonged, and the life quality is improved, so that the traditional Chinese medicine or the effective components have very key significance.
Lignum sappan, also known as Sufang wood. Is dried heartwood of Caesalpinia sappan L (Leguminosae), and mainly contains compounds such as hematoxylin, brazilin, and protosappanin. The traditional Chinese medicine believes that the traditional Chinese medicine has the effects of clearing blood heat and regulating menstruation and is used for relieving symptoms such as menstrual pain and liver blood increase. Early studies have confirmed that the ethanol extract of lignum sappan and the monomer component, protosappan A, have the effect of resisting transplant rejection, and play the role of immunosuppression by regulating and controlling multiple links such as the activity of immune cells and the secretion of cytokines. The method for extracting the protosappanin A naturally is limited by difficult operation, large workload and low yield, so the method also becomes a difficult point in scientific research and clinical application. In subsequent studies, we obtained derivatives of protosappanin A by chemical synthesis, confirmed that the derivatives have immunosuppressive effects, and have obtained patent protection (ZL 201010112431.9). While the immunosuppressive effects of the protosappanin A and the derivatives are deeply discussed, the protosappanin A derivatives are also found to have the effect of protecting heart damage caused by chemotherapeutic drugs.
Disclosure of Invention
The invention aims to provide application of a hematoxylin A derivative in preparing a medicine for treating or preventing cardiac damage caused by chemotherapy drug treatment.
The chemical structural formula of the protosappanin A derivative is shown as a general formula I:
wherein: r1Is C1-4Alkyl groups of (a); r2Is C1-4Alkyl group of (1).
Specific methods for producing the orthohematoxylin a derivative represented by the general formula i are described in patent application No. 201010112431.9 entitled "orthohematoxylin a derivative, and methods for producing and using the same".
Among them, preferred is a compound of the formula I wherein R1Is methyl; r2Is methyl, namely the protosappanin A derivative is 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone.
Wherein, the chemotherapy drug is preferably adriamycin.
Preferably, the cardiac damage comprises apoptosis and fibrosis of cardiac muscle cells, decreased cardiac function, increased brain natriuretic peptide concentration and increased oxidative stress level.
The invention proves that the protosappanin A derivative has the effects of protecting the heart and improving the cardiotoxic damage caused by the chemotherapeutic drug adriamycin by using the 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone for the heart damage caused by the chemotherapeutic drug, has small toxic and side effects, and is a heart protection drug with development prospect. The development of traditional Chinese medicines and the finding of new heart protection medicines, in particular to protection medicines for heart damage caused by chemotherapy medicines, have Chinese characteristics, accord with Chinese situations, and are a chance to push traditional Chinese medicines to the world. The traditional Chinese medicine has rich resources, high availability, small side effect, few toxic and side effects and low price. Therefore, the traditional Chinese medicine or the effective components with the heart protection effect are searched, the action mechanism of the traditional Chinese medicine or the effective components is deeply researched, the pain and the economic burden of patients can be relieved, more patients can receive chemotherapy, the life of the patients is prolonged, and the life quality is improved, so that the traditional Chinese medicine or the effective components have very key significance.
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FIG. 1 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on cardiac function in model rats;
wherein, FIG. 1A is a graphical representation of the effect of doxorubicin on heart function in model rats; FIG. 1B is a graphical representation of the effect of low doses of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on cardiac function in model rats; FIG. 1C is a graphical representation of the effect of high doses of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on cardiac function in model rats;
FIG. 2 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on the heart index of model rats;
FIG. 3 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) propanone on the concentration of model rat brain natriuretic peptides;
FIG. 4 is a graphic representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on the change in model rat CK-MB;
FIG. 5 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on changes in cTNI in model rats;
FIG. 6 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on myocardial fibrosis in model rats;
FIG. 7 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on model rat type III collagen;
FIG. 8 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on Caspase-3 activity in model rats;
FIG. 9 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on apoptosis in myocardial cells of model rats;
FIG. 10 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone on the expression levels of model rat Bcl-2 mRNA;
FIG. 11 is a graphic representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on the change in SOD in model rats;
FIG. 12 is a graphical representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on model rat MDA changes;
FIG. 13 is a graphic representation of the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) propanone on blood conventions for model rats;
FIG. 14 is a graph showing the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone on blood biochemistry of model rats.
Detailed Description
The above and further features and advantages of the present invention are explained in more detail below with reference to examples. It should be understood that the following examples are illustrative of preferred embodiments of the present invention only and are not intended to limit the scope of the present invention, and that various changes and modifications in the technical solutions of the present invention by those skilled in the art may be made without departing from the spirit of the present invention, which is defined by the appended claims.
Example 11 Effect of- (2 ', 4, 4', 5-Tetramethoxy-2-Biphenyl) propanone on improving cardiac function in rats treated with Adriamycin
The experimental method comprises the following steps:
1. establishment of rat adriamycin-induced myocardial injury model
After the adriamycin is diluted to 1mg/ml concentration by normal saline, the adriamycin is injected into the abdominal cavity of a rat to ensure that the dose of the adriamycin is 2.5mg/kg/w, and a myocardial damage model can be obtained after 6 weeks.
2. Animal grouping and administration
The model animals were given different drugs for intragastric administration, and were randomized into three groups: (1) the control group is subjected to intragastric administration by using normal saline; (2) compound low dose group: gavage with 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone (5 mg/kg/w); (3) compound high dose group: 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone (25mg/kg/w) was administered for intragastric administration. Each of the above groups of animals was dosed the day before doxorubicin treatment.
3. Observation of general State after administration
The observation includes the observation of the mental development status, diet and activity status, weight change, and normal urine and feces properties of the rats in the control group and the compound group.
4. Color ultrasound and echocardiography: ultrasonic testing of model rats (6 weeks), 10% chloral hydrate anesthesia, precordial skin preparation, supine position, using a multifunctional ultrasonic diagnostic apparatus, using a 10S probe (probe frequency 11.0 MHz). Taking a long-axis section of the left ventricle beside the sternum, and measuring the Left Ventricular End Systolic Diameter (LVESD), the Left Ventricular End Diastolic Diameter (LVEDD) and the left ventricular Ejection Fraction (EF) respectively.
5. Calculating the heart index: immediately weighing the rat after color ultrasonography and recording, immediately dissecting and taking out the heart to weigh the heart, weighing the heart wet weight/the rat weight, and calculating the numerical value.
6, monitoring plasma brain natriuretic peptide, namely rapidly splitting the abdominal cavity of a rat after color ultrasonography is finished, separating the inferior vena cava, slowly drawing blood at a constant speed, injecting the blood into a procoagulant tube, standing for 20min, centrifuging for 5min at 4 ℃ and 4000rpm, and collecting supernatant to store at-80 ℃ for later use. The detection is carried out strictly according to the steps of the BNP kit.
The experimental results are shown in fig. 1, 2 and 3, and prove that 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone reduces the degree of cardiac function damage caused by adriamycin, reduces the concentration of brain natriuretic peptide, and has statistical difference compared with the control group. Proves that the 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone is an effective heart protection medicament and can obviously improve the myocardial toxicity damage induced by the adriamycin.
Example 21 Effect of 2 ', 4, 4', 5-Tetramethoxy-2-Biphenyl) acetone on myocardial injury and fibrosis in rats
The rat doxorubicin-induced myocardial injury model was established, and animal groups and dosing were as in example 1.
The detection indexes and the method are as follows:
1. detection of cardiac myogenases and troponins: three groups of rats were treated immediately after 6 weeks of administration, and blood was collected by removing eyeballs, and the operation method and procedure were performed according to the instructions of the myocardial enzyme and troponin kit.
Masson staining: the experimental process comprises paraffin section dewaxing, hematoxylin staining, phosphomolybdic acid aqueous solution differentiation for 3-5min, soaking in glacial acetic acid aqueous solution, dehydration, xylene transparency and neutral resin sealing.
Detection of type iii collagen: treating the rat immediately after 6 weeks of administration, extracting the total RNA of the ventricular muscle tissue of the rat by using a Trizol method, and performing an operation method according to the instruction of a kit, wherein the reaction program is preheating at 95 ℃ for 1 min; repeating the steps for 40 times at 95 deg.C for 15s, 58 deg.C for 20s, and 72 deg.C for 45 s; the dissolution curve is 60 ℃ to 95 ℃, the temperature is increased by 1 ℃ every 20s, the reactants comprise 5 mul of 2 xqqPCR mixed solution, 1 mul of primer working solution, 1 mul of qPCR template, 2.8 mul of double distilled water, and the amplification primers:
5'-TGTCCACAGCCTTCTACACCT-3' (upstream primer),
5'-TAGCCACCCATTCCTCCG-3' (downstream primer).
The results of the analysis and the experimental results are shown in fig. 4, 5, 6 and 7, which indicate that 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone can reduce myocardial damage and fibrosis induced by adriamycin, and the effect is dose-dependent.
Example 31 Effect of (2 ', 4, 4', 5-Tetramethoxy-2-Biphenyl) propanone on inhibiting Adriamycin induced apoptosis in myocardial cells
The experimental method comprises the following steps:
(1) culturing the myocardial cells: taking the core tip, washing with pre-cooled D-Hank's solution for 3 times, and cutting the heart to about 1 cubic millimeter; treating myocardial tissue with pancreatin (0.0625%) at 37 deg.C for 5min × 5 times, increasing for 1min, repeating for 5 times, repeating for 8 min, naturally precipitating for the first time, discarding supernatant, and naturally precipitating for each time; adding the collected supernatant into DMEM culture solution with the same volume, beating by blowing, uniformly mixing, gently moving, centrifuging at 1000 r/min for 10min, and repeating for 3 times. Cells were divided into three groups, the doxorubicin-treated group: ADR was added to a final concentration of 8. mu. mol/L for the low dose group of compounds: doxorubicin treatment was accompanied by the addition of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone (5nM) and a high dose group of compounds: doxorubicin treatment was performed while adding 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenylyl) acetone (25nM), stimulating for 12h, and observing cell morphology under microscope.
(2) Detecting the apoptosis level: after 12 hours, the culture medium was removed from the three groups, and the groups were washed 1 or 2 times with PBS, and the specific procedures were carried out according to the Caspase-3 activity assay kit, where absorbance A was measured at λ 405nm for each group, and A (administered group)/A (blank group) was calculated to evaluate Caspase-3 activity.
(3) Flow detection of apoptosis: cells growing adherently need to be digested by 0.25% pancreatin without EDTA and collected, the cells are collected by centrifugation at 2000r/min for 5-10 minutes at room temperature, precooled PBS (4 ℃) is added for collecting the cells, the cells are resuspended once, the cells are centrifuged at 2000rpm for 5-10 minutes, the cells are washed, 300 mu L of 1 XBinding Buffer suspension cells are added, 5 mu L of Annexin V-FITC is added for even mixing, the cells are protected from light and incubated for 15 minutes at room temperature, 5 mu L of PI staining is added before loading the machine for 5 minutes, and 200 mu L of 1 XBinding Buffer is added for detection before loading the machine.
(4) Detecting apoptosis related genes by PCR: (Bcl-2)
Extracting total RNA of the myocardial tissue according to the instruction of the RNA extraction kit. Reverse transcription of total RNA the protocol for M-M LV reverse transcriptase was followed. After inactivation of M-M LV reverse transcriptase at 70 ℃ for 10min, 100. mu.L of the solution was diluted with PCR water. PCR amplification was performed using 5. mu.L of the reverse transcription product as a template. The primer sequence is as follows: 5 'TCCATT ATA AGC TGT CACAG 3' (upstream primer); 5 'GAAGAGTTCCTCCACCAC 3' (downstream primer). The total volume of the PCR reaction was 25. mu.L: reverse transcription product 5. mu.L, 10pmol each of upstream and downstream primers 2. mu.L, 5mmol/LdN TP 1. mu.L, 10 Xreaction buffer 2.5. mu.L, 25mmol/L MgCl21.5. mu.L of Taq DNA polymerase, 1U of Taq DNA polymerase and 10.75. mu.L of PCR water. And (3) PCR amplification process: repeating at 94 deg.C, 50 deg.C and 72 deg.C for 1min respectively for 1 time; repeating the steps at 94 deg.C, 55 deg.C and 72 deg.C for 1min respectively for 35 times; 72 ℃ for 15 min. And analyzing and calculating the result.
The experimental results are shown in fig. 8, 9 and 10, and the results show that 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone can obviously inhibit the effect of adriamycin on inducing myocardial apoptosis, and further confirm the heart protection effect of the compounds.
Example 41- (2 ', 4, 4', 5-Tetramethoxy-2-Biphenyl) propanone inhibition of Adriamycin induced increased myocardial cell oxidative stress levels
The rat doxorubicin-induced myocardial injury model was established, and animal groups and dosing were as in example 1.
The detection indexes and the method are as follows:
detecting the contents of SOD and MDA: after 6 weeks of dosing, after sacrifice of the rats, about 0.5g of cardiac tissue was taken, washed with physiological saline to wash away blood, wiped dry with filter paper, weighed and sheared as soon as possible. The tissue was ground thoroughly in a homogenizer. Centrifuging 10% tissue homogenate at 3000 r/min in a low temperature centrifuge for 10-15 min. Collecting supernatant, and measuring the content of MDA and SOD in heart. Each step of operation was performed according to the kit instructions.
The experimental results are shown in fig. 11 and 12: the kit determines the contents of MDA and SOD, and the contents of MDA and SOD are greatly reduced after 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone is applied, so that the improvement of the oxidative stress level caused by 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone adriamycin is proved to have a certain inhibiting effect.
Example toxic side effects of 51- (2 ', 4, 4', 5-Tetramethoxy-2-Biphenyl) propanone
The rat doxorubicin-induced myocardial injury model was established, and animal groups and dosing were as in example 1.
The experimental method comprises the following steps: the observation includes the observation of the mental state, diet and activity, weight change, and normal urine and feces properties of the rats in the control group and the compound group. Anaesthetizing after 7 days, opening the abdomen, collecting 4-5ml of blood from inferior vena cava, performing routine and biochemical examination of blood, taking liver and kidney for pathological examination, and determining the effect of 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone.
The experimental results are shown in fig. 13 and 14: after the 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone is applied, the conventional and biochemical indexes of the rat blood are not obviously changed. And the hepatorenal pathology of the 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) acetone is not significantly changed.
Claims (2)
1. Use of a derivative of protosappanin a for the manufacture of a medicament for the treatment or prevention of cardiac damage resulting from doxorubicin therapy, said derivative of protosappanin a being 1- (2 ', 4, 4', 5-tetramethoxy-2-biphenyl) propanone.
2. The use of claim 1, wherein said cardiac damage comprises apoptosis and fibrosis of cardiac muscle cells, decreased cardiac function, increased brain natriuretic peptide concentration, and increased levels of oxidative stress.
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Non-Patent Citations (4)
| Title |
|---|
| Protosappanin A induces immunosuppression of rats heart transplantation targeting T cells in grafts via NF-κB pathway;Jian Wu 等;《Naunyn-Schmiedeberg"s Archives of Pharmacology》;20091119;83-92 * |
| The immunosuppressant Protosappanin A diminished recipient T cell migration into allograft via inhibition of IP-10 in rat heart transplant;Maomao Zhang 等;《Plos one》;20140505;第9卷(第5期);1-8 * |
| 原苏木素A对心脏移植后大鼠T淋巴细胞亚群的影响;程露杨 等;《哈尔滨医科大学学报》;20090430;第43卷(第2期);134-136 * |
| 苏木醇提物抗大鼠心脏移植排斥反应有效成分分析;吴健 等;《哈尔滨医科大学学报》;20071231;第41卷(第6期);615-620 * |
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