20 results about "Rat myocardium" patented technology

The invention discloses a medicine for treating or relieving heart failure, the medicine comprises an estrogen compound, and the estrogen compound is preferably mestraanol. According to the invention, verapamil hydrochloride is used for inducing and establishing the chronic heart failure model of zebrafish, and direct exposure of the estrogen compound MESTRANOL is carried out on a zebrafish embryo with heart failure, so that the heart failure of zebrafish is relieved. The phenotype of zebrafish is observed and analyzed, and physiological data, gene expression quantity related to heart failure and key events causing heart failure in rat H9c2 myocardial cells, such as ROS level and cell apoptosis, are counted; the estrogen compound MESTRANOL is innovatively found and proved to be capable of relieving heart rate decline, venous sinus extravasated blood, pericardial cavity enlargement and heart cyclization abnormity caused by heart failure, and has more excellent drug effects compared with positive drugs E2 and G1, so that a foundation is laid for developing new drugs for treating heart failure.

The invention discloses an NLRP3 inhibitor as well as a preparation method and application thereof. Specifically, the invention relates to a compound shown as a formula (NLRP3i-3) or a pharmaceutically acceptable salt thereof, the formula (I) is COCCNc1nc2c (c (= O) n (C) c (= O) n2C) n1Cc1cc (OC) ccc1N, and the chemical name is 8-((4-amino-2-methoxybenzyl)-7, 9-dimethyl-7, 9-dihydro-8H-purine-6, 8-diketone. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and application of the compound in preparation of drugs for preventing and / or treating NLRP3-mediated diseases. The disease is preferably myocardial ischemia reperfusion injury. Experimental results show that the compound provided by the invention has excellent NLRP3 inhibitory activity (IC50lt, 100nM), and has high selectivity to NLRP3 inflammasomes; good pharmacokinetic characteristics are achieved in a rat body, and the bioavailability is high; in myocardial ischemia reperfusion injury models of mice and rats, the composition can significantly reduce myocardial infarction area, reduce myocardial enzyme level, alleviate inflammatory response and improve heart function; preliminary toxicological evaluation shows that the safety is good. Therefore, the compound disclosed by the invention is expected to be developed into a novel medicine for treating NLRP3 related diseases such as myocardial ischemia-reperfusion injury.

The present application discloses the use of thiolated hyaluronic acid or its salt in myocardial ischemia-reperfusion injury, and belongs to the field of biomedical technology. In this use, the degree of substitution of the synthesized thiolated hyaluronic acid or its salt thiol can reach 10%-40%. The antioxidant capacity of 5mg / ml thiolated hyaluronic acid or its salt can reach more than 50%; in the H9C2 cardiomyocyte SI / RI model, HA-SH can protect H9C2 cardiomyocytes, and can significantly reduce the oxidative stress damage in the SI / RI model; in the constructed rat myocardial ischemia-reperfusion injury model, HA-SH can reduce the oxidative stress damage, apoptosis and inflammatory response caused by myocardial ischemia-reperfusion by regulating the Nrf2 signaling pathway and the HO-1 signaling pathway, reduce the iron mortality rate, and play a role in protecting the heart. The present application provides a new drug development approach, which is of great significance in the field of biomedical technology.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to 2, 3-dihydrobenzofuran derivatives and application thereof in preparation of drugs for treating cardiovascular and cerebrovascular diseases. The 2, 3-dihydrobenzofuran derivative disclosed by the invention has a protective effect on H9c2 rat myocardial cell injury caused by H2O2, and can improve the cell survival rate and reduce the LDH release rate; meanwhile, the area of myocardial infarction of mice after myocardial infarction can be remarkably reduced, and the compound has an obvious myocardial protection effect, can be developed into drugs for resisting cardiovascular and cerebrovascular diseases and has a good application prospect. When the 2, 3-dihydrobenzofuran derivative and the luteolin are combined for use, a synergistic effect on treatment of cardiovascular and cerebrovascular diseases is achieved, the synergistic effect of the 2, 3-dihydrobenzofuran derivative and the luteolin can improve the protection effect on the heart, and after the 2, 3-dihydrobenzofuran derivative and the luteolin are combined for use, compared with a single drug, the damage of H2O2 to cells is obviously reduced, and the treatment effect on cardiovascular and cerebrovascular diseases is improved. The cell survival rate is obviously increased, and the LDH release rate is obviously reduced.

The invention discloses a pharmaceutical composition containing radix astragali, radix salviae miltiorrhizae, radix salviae miltiorrhizae and fructus schizandrae and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine, the pharmaceutical composition containing radix astragali, radix salviae miltiorrhizae, radix salviae miltiorrhizae and fructus schizandrae is prepared from the following raw materials in parts by weight: 30-50 parts of radix astragali, 15-30 parts of radix salviae miltiorrhizae, 15-30 parts of radix codonopsis, 15-30 parts of radix pseudostellariae, 3-5 parts of fructus schizandrae and 10-15 parts of radix et rhizoma rhei. Preferably, the oral medicine dosage forms capable of being prepared comprise hard capsules, tablets and granules. According to the application disclosed by the invention, the expression levels of p38MAPK, JNK and ERK proteins, c-fos mRNA and c-jun mRNA of myocardial tissues of rats in a medicine group are lowest, so that the medicine disclosed by the invention can be used for inhibiting the activity of an MAPK signal channel of the myocardial tissues and inhibiting the expression of related protooncogenes c-fos and c-jun so as to inhibit myocardial fibrosis. Therefore, the medicine can effectively improve the cardiac function of a DCM model rat and relieve myocardial damage, and the effect of the medicine is related to inhibition of MAPK signal channel activity.

The invention relates to the technical field of medical animal model construction, in particular to a construction method and application of a cardiomyopathy animal model induced by a circulating system. According to the invention, the Abeta25-35 is injected into the adventitia, so that the animal model of the cardiomyopathy induced by the Abeta25-35 through the tissue fluid circulatory system of the adventitia is constructed in the SD rat for the first time. In the model, A beta 25-35 is subjected to myocardial perfusion through lower limb vascular adventitia to induce myocardial diffuse fibrosis and ejection fraction reduction of SD rats, which are in accordance with epidemiological research data. The model can be used for subsequently researching the pathogenic mechanism of A beta25-35 induced cardiomyopathy and a novel treatment method taking vascular adventitia tissue fluid transmission as a way, and also provides a brand new view angle for researching the pathogenic mechanism of AD or cerebrovascular diseases and a diagnosis and treatment method.

The application relates to application of siRNA-OTUB1 in preparation of drugs for preventing or treating myocardial cell hypertrophy, and belongs to the biomedical technical field.The nucleotide sequence of the OTUB1 gene is shown as SEQ ID NO.1, and the targeted nucleotide sequence of the siRNA-OTUB1 for specifically interfering with the expression of the OTUB1 gene is shown as SEQ ID NO.2 or SEQ ID NO.3.The application innovatively proposes a strategy for preventing or treating myocardial cell hypertrophy by taking deubiquitinase OTUB1 as a core target point and by interfering with the expression thereof.In a myocardial cell experiment of a milk rat, the application of the designed siRNA-OTUB1 can effectively reduce the expression levels of OTUB1 mRNA and OTUB1 protein, and further reduce the degree of myocardial cell hypertrophy.Based on the finding, the OTUB1 gene can be developed as a novel treatment target point for myocardial cell hypertrophy, is used for designing a targeted drug, and provides a new technical thought for precise treatment of myocardial hypertrophy.

This invention relates to the field of medical animal model construction technology, and in particular to a method for constructing an animal model of cardiomyopathy induced by the circulatory system and its application. This invention, through adventitia-35 injection, establishes for the first time an animal model of "Aβ25-35-induced cardiomyopathy via the adventitia-35 circulatory system" in SD rats. In this model, Aβ25-35 perfusion via the adventitia-35 myocardium of the lower limbs induces diffuse myocardial fibrosis and a decrease in ejection fraction in SD rats, consistent with epidemiological data. This model can be used to further study the pathogenic mechanism of Aβ25-35-induced cardiomyopathy and novel treatment methods using adventitia-35 transport as a pathway, while also providing a new perspective for studying the pathogenic mechanisms and diagnostic and treatment methods of AD or cerebrovascular diseases.

The application belongs to the technical field of medicine, and particularly relates to application of acacetin or 6-hydroxyflavone in preparation of anti-angina pectoris drugs, and aims to solve the problems of adverse reactions such as blood pressure drop, reflex tachycardia and the like caused by non-selective vasodilation of existing anti-angina pectoris drugs, wherein the drug improves myocardial blood supply by selectively dilating coronary vessels of the heart, wherein acacetin dilates coronary vessels of the heart by inhibiting cardiac coronary vessel myosin light chain kinase and activating myosin light chain phosphatase, and 6-hydroxyflavone dilates coronary vessels of the heart by inhibiting protein kinase C and enhancing myosin light chain phosphatase activity; and the acacetin or 6-hydroxyflavone significantly reduces the symptoms of myocardial ischemia of rats caused by isopropyl adrenaline, improves characteristic ECG abnormal changes of angina pectoris, does not affect heart rate and systemic blood pressure, and is safer, thereby providing a potential drug selection for anti-angina pectoris treatment.

The present invention belongs to the field of pharmaceutical technology, and specifically discloses the application of a SARMs compound EG-017 containing an ester group aromatic propanamide and its metabolite EG-2 in the preparation of anti-SARS-CoV-2 drugs, inhibiting multi-organ damage such as lung and heart caused by SARS-CoV-2, and treating pulmonary fibrosis. The in vitro anti-SARS-CoV-2 activity and cytotoxicity of the compound were evaluated by IFA, which well verified that EG-017 has obvious inhibitory activity on the replication of SARS-CoV-2 βCoV / KOR / KCDC03 / 2020 strain in Vero cells, indicating its application prospect in the preparation of anti-SARS-CoV-2 drugs; the experiment also showed that EG-017 can well inhibit the cytotoxicity of high-concentration rapamycin to cells; the MTT method was used to verify that EG-017 can significantly improve the survival rate of rat cardiomyocytes. The potential application value of EG-017 and its metabolite in the treatment of lung lesions caused by SARS-CoV-2 and other lung diseases such as pulmonary fibrosis caused by other reasons was verified through the experiment on the effect of EG-017 on the fibrosis process of TGF-β1-induced A549 lung cancer cells.

The invention relates to application of siRNA-OTUB1 in preparation of a medicine for preventing or treating myocardial cell hypertrophy, and belongs to the technical field of biomedicine. The nucleotide sequence of the OTUB1 gene is as shown in SEQ ID NO.1, and the target nucleotide sequence of the siRNA-OTUB1 for specifically interfering with the expression of the OTUB1 gene is as shown in SEQ ID NO.2 or SEQ ID NO.3. The invention further discloses the application of the siRNA-OTUB1 gene. The invention innovatively provides a strategy for preventing or treating myocardial cell hypertrophy by intervening the expression of the deubiquitinating enzyme OTUB1 serving as a core target. In a myocardial cell experiment of a milk rat, by applying the siRNA-OTUB1 designed by the invention, the expression level of OTUB1 mRNA and OTUB1 protein can be effectively reduced, so that the hypertrophy degree of myocardial cells is reduced. Based on the discovery, the OTUB1 gene can be developed into a novel therapeutic target for myocardial hypertrophy, is used for designing targeted drugs, and provides a new technical thought for precise treatment of myocardial hypertrophy.

The application belongs to the technical field of biological medicine, and particularly relates to a biomarker and application thereof. The application finds that the expression level of a specific subtype of a nicotine acetylcholine receptor of an arrhythmia patient is significantly lower than that of a sinus rhythm population, and the expression of the nicotine acetylcholine receptor in ischemia / reperfusion injury myocardium of a rat and myocardium of a heart failure patient also shows a significant downward trend. Further research finds that the expression loss of the specific subtype of the nAChR significantly increases the risk of arrhythmia. In combination with animal experiment results and human clinical data, it can be seen that the expression defect of the endogenous cholinergic system is closely related to fatal arrhythmia.

The invention belongs to the technical field of biology, and discloses an engineering mesenchymal stem cell transformation method based on cholesterol anchoring and antibody modification and application of the engineering mesenchymal stem cell transformation method. The rigidity of the cell membrane of the MSCs is reduced by regulating and controlling the cholesterol level on the cell membrane, and the MSCs are promoted to pass through narrow capillaries with higher deformation capacity, so that the non-specific aggregation in the lung is reduced. Besides, exogenous modified cholesterol is used as an anchor point on a cell membrane, specific antibodies aiming at different damaged tissues are modified on the surfaces of the MSCs by means of DNA self-assembly, and the engineered MSCs are constructed. Experimental results show that in a mouse acute kidney injury and colitis model and a rat myocardial infarction model with higher blood flow shearing force, the engineered MSCs for modifying cholesterol and a specific antibody can reduce retention in the lung and improve homing efficiency of damaged tissues.

The invention relates to the technical field of biomedicine, in particular to application of a Pxdc1 gene in regulation and control of exosome secretion. The key effect of Pxdc1 in induction of cell exosome formation and secretion is disclosed for the first time, and a new strategy is provided for treatment of cardiovascular diseases. By constructing Pxdc1 overexpression plasmids or virus vectors, secretion of exosomes in 293T cells and primary rat myocardial cells is successfully promoted, and a foundation is laid for preparing reagents or drugs for regulating and controlling exosome secretion. Meanwhile, RNA interference is utilized to reduce Pxdc1 expression, exosome secretion is effectively inhibited, and the core regulation effect of Pxdc1 is further verified. The invention not only deepens the understanding of the Pxdc1 gene function, but also provides an innovative thought for the cell-free therapy and drug delivery system of cardiovascular diseases, and has important scientific value and application potential.

Disclosed is a drug for treating or alleviating heart failure, which comprises an estrogenic compound. The estrogenic compound is preferably mestranol. By means of induction with verapamil hydrochloride, a zebrafish model of chronic heart failure is established. Zebrafish embryos with heart failure are directly exposed to the estrogenic compound MESTRANOL, resulting in the alleviation of heart failure in the zebrafish. By means of observation and analysis of zebrafish phenotypes and statistical analysis of physiological data and expression levels of heart failure-related genes, as well as key events causing heart failure in rat H9c2 cardiomyocytes such as ROS level and apoptosis, it is innovatively discovered and confirmed that the estrogenic compound MESTRANOL can alleviate decreased heart rate, venous sinus congestion, pericardial cavity enlargement, and abnormal cardiac looping caused by heart failure, and has superior efficacy to positive drugs E2 and G1, thereby laying a foundation for developing new drugs for treating heart failure.

The invention discloses conductive hydrogel based on bioactive polypeptide as well as a preparation method and application of the conductive hydrogel, and belongs to the technical field of biological medicines. The invention discloses conductive hydrogel based on bioactive polypeptide. The conductive hydrogel is beneficial to stable transmission of an electric signal, regulation of the level of active oxygen in a body and synchronous contraction of myocardial cells. And a stable platform is provided for continuous release of the angiogenic peptide. In-vitro research shows that the compound has excellent cell compatibility, can remarkably promote endothelial cell proliferation, and has efficient active oxygen scavenging capacity. In a rat myocardial infarction model, the heart function of a mouse is remarkably improved by the composite hydrogel. Histological and immunohistochemical tests further prove the therapeutic effect of the traditional Chinese medicine composition. Therefore, the prepared composite hydrogel can adjust the myocardial microenvironment and electrical activity at the same time, so that the recovery process of myocardial infarction is accelerated, and the composite hydrogel has wide application potential in the aspect of treating myocardial infarction.

The application provides application of a traditional Chinese medicine composition in preparation of a medicine for treating cardiac senility, and the traditional Chinese medicine composition is composed of Semen Euryae, Fructus Lycii, Schisandra chinensis, Cnidium, Chamaerops, Semen Allii Tuberosi, Dipsacus asper, Cistanche, Rehmannia glutinosa, Cyathula officinalis, Herba Epimedii, Rubus chingii, Ginseng, Cornu Cervi Pantotrichum, sea horse and Fructus Meliae Toosendan. Test results show that the medicine can significantly reduce the collagen content of myocardial tissue of HFpEF rats, reduce the degree of myocardial fibrosis, inhibit left ventricular remodeling, thereby improving the cardiac function of the rats, preventing and treating heart failure with preserved ejection fraction, and treating cardiac senility with remarkable effects.

The invention relates to the technical field of biology, and particularly discloses a preparation method and application of serum exosomes after electroacupuncture, and the method comprises the following steps: establishing a rat myocardial ischemia reperfusion injury model; applying electroacupuncture stimulation with current of 1mA, frequency of 2Hz and sparse and dense waves to'neiguan 'acupoints on two sides of the rat; serum is collected, and exosomes are extracted through a differential centrifugation method and an ultracentrifugation method; identifying form, particle size and surface marker proteins CD9 and CD81 of the extracted exosome by using a transmission electron microscope and a nanoflow detection technology; the exosome can be internalized by H9c2 myocardial cells, the survival rate of hypoxia / reoxygenation damaged myocardial cells is improved, and the levels of lactic dehydrogenase, creatine kinase and creatine kinase isoenzyme in cell supernatant are reduced. According to the scheme provided by the invention, a novel post-acupuncture serum exosome for treating myocardial ischemia reperfusion injury is provided, and the exosome effectively plays an acupuncture-like role in a treatment process, so that an effect of relieving myocardial ischemia reperfusion is achieved.

The present invention discloses a Chinese medicine composition for preventing and treating coronary heart disease and angina pectoris and a preparation method thereof, belonging to the field of Chinese medicine preparations. The Chinese medicine composition is prepared from 17 Chinese medicinal herbs: astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, polygonatum, epimedium, kudzu root, angelica, salvia miltiorrhiza, honeysuckle, kelp, kelp, oyster, and immature bitter orange. The composition of the present invention is well-matched and synergistic, and has the effects of invigorating qi and activating blood circulation, resolving phlegm and unblocking meridians. It is suitable for treating chest pain caused by qi and yin deficiency, phlegm and blood stasis, coronary heart disease, and angina pectoris, as well as pharmacodynamic tests. Pharmacodynamic tests show that the Chinese medicine composition of the present invention can significantly prolong the hypoxia tolerance time of mice, has a certain antagonistic effect on acute myocardial ischemia caused by vasopressin in rats, has a significant reducing effect on ST segment elevation caused by coronary artery ligation in rats, can significantly reduce the range of myocardial infarction caused by coronary artery ligation, and has a reducing effect on hyperlipidemia in rats fed a high-fat diet.

The application belongs to the field of medicine, and particularly relates to a use of a traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating chronic heart failure. Specifically, the traditional Chinese medicine composition is prepared from Radix Polygoni Multiflori, Aloe, Semen Cassiae, Radix et Rhizoma Ginseng, Fructus Lycii, Colla Corii Asini, Fructus Aurantii Immaturus and Rhizoma Atractylodis. The pharmacodynamic experiment results show that the traditional Chinese medicine composition can obviously improve the state of rats caused by injection of doxorubicin hydrochloride, such as dry and withered fur, lazy and lying, inactivity, reduced food intake, shortness of breath and the like; can obviously increase the survival rate of the rats; can obviously increase the ejection fraction and shorten fraction; pathological observation shows that the traditional Chinese medicine composition can obviously reduce the myocardial cell remodeling of the rats with chronic heart failure, which indicates that the traditional Chinese medicine composition has a definite effect of treating chronic heart failure, and has a potential application value in preparation of a medicine for preventing and / or treating chronic heart failure.