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Application of recombination human fibroblast growth factor-21 in preparation of medicament for preventing and treating ischemic arrhythmia

A technology of human fibroblasts and growth factors, applied in the field of biomedicine, can solve the problems of poor safety and can not effectively improve the imbalance of ion channel function, and achieve the effect of reducing the possibility, preventing the complications of heart failure and reducing the incidence rate

Inactive Publication Date: 2017-02-22
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional antiarrhythmic drugs still have many deficiencies in clinical treatment: (1) An antiarrhythmic drug only selectively excites or blocks a specific type of ion channel, affecting the duration of myocardial action potential and effective refractory period , so as to exert its antiarrhythmic effect, but its mechanism of action cannot effectively improve the pathophysiological basis of ion channel function imbalance caused by cardiac electrical remodeling, so it is still in the stage of symptomatic treatment; (2) the traditional four types of antiarrhythmic Arrhythmia-inducing side effects can occur in long-term or excessive use of arrhythmic drugs, so the safety of long-term use is poor
Among them, FGF21 has cardioprotective effects in inhibiting myocardial cell apoptosis and resisting ischemic injury in heart failure, myocardial hypertrophy, myocardial oxidative stress injury, myocardial ischemia and diabetic heart disease animal models, but there is no research yet Discovery of the role of FGF21 in the development of cardiac arrhythmias

Method used

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  • Application of recombination human fibroblast growth factor-21 in preparation of medicament for preventing and treating ischemic arrhythmia
  • Application of recombination human fibroblast growth factor-21 in preparation of medicament for preventing and treating ischemic arrhythmia
  • Application of recombination human fibroblast growth factor-21 in preparation of medicament for preventing and treating ischemic arrhythmia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1, antiarrhythmic effect of rhbFGF21

[0037] 1. rhbFGF21 reduces the incidence of arrhythmia in the acute phase (15mins) and chronic phase (1 week, 4 weeks) of myocardial infarction rats

[0038] 1) Establishment of myocardial infarction rat model: In this experiment, SD rats of 180±10 g were selected, anesthetized by intraperitoneal injection of 3% amobarbital sodium, connected to a small animal ventilator, and ligated the left anterior descending coronary artery after thoracotomy. A rat model of myocardial infarction was established. Experimental animals were divided into sham operation group (Sham group), only thoracotomy without ligation of coronary artery; myocardial infarction group (MI group), thoracotomy and coronary artery ligation; myocardial infarction administration group (MI+rhbFGF21 group), thoracotomy ligation Intraventricular injection of rhbFGF21 (7μg / kg) 1 hour before coronary artery and intraperitoneal administration (7μg / kg) every day af...

Embodiment 2

[0043] Example 2. The protective effect of rhbFGF21 on the heart of rat model of myocardial infarction

[0044] 1. Establishment of myocardial infarction rat model: the method is the same as that described in Example 1.

[0045] 2. Observation results:

[0046] 1) Protective effect of rhbFGF21 on cardiac function after myocardial infarction

[0047] Cardiac function and left ventricular structural changes were detected by echocardiographic technique before operation and at 1 week and 4 weeks after operation (see image 3 ). The left ventricular volume and ventricular wall thickness of the rats in the Sham group had no significant changes at 1 week and 4 weeks after the operation compared with those before the operation; the left ventricular volume of the rats in the MI group was significantly expanded at 1 week after myocardial infarction compared with that before myocardial infarction, and the ventricle The wall becomes thinner; the volume of the left ventricle at 4 weeks ...

Embodiment 3

[0052] Example 3. The effect of rhbFGF21 on the viability of cardiomyocytes and fibroblasts

[0053] 1. Cell culture and experimental grouping:

[0054] Adult rat ventricular myocyte cell line (H9C2) and primary cultured rat cardiac fibroblasts were pretreated with rhbFGF21 (25, 50, 75, 100, 200, 400 ng / ml) for 2 hours at 37°C, 5% CO 2 Cells were collected after 24 hours of incubation in an incubator for MTT assay.

[0055] 2. Observation results:

[0056] Cardiomyocyte viability was detected by MTT method. It was shown that rhbFGF21 (25, 50, 75 and 100ng / ml) significantly increased the viability of cardiomyocytes and promoted the proliferation of cardiomyocytes (see Figure 7 A). At the same time, primary cultured rat fibroblasts were incubated with different concentrations of rhbFGF21 for 48 hours to detect the viability of fibroblasts by cell counting and MTT method. The results showed that 75ng / mlrhbFGF21 showed a tendency to inhibit the proliferation of fibroblasts, ...

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Abstract

The invention discloses application of a recombination human fibroblast growth factor-21 (rhbFGF21) in preparation of a medicament for preventing and treating ischemic arrhythmia. The study of the invention finds that preventive administration of the rhbFGF21 is performed on a myocardial infarction animal model before myocardial infarction, so that the occurrence rate of acute-stage arrhythmia after myocardial infarction can be obviously reduced; preventive administration of the rhbFGF21 is performed on the infarction animal model before myocardial infarction, and one-week continuous intraperitoneal injection administration of the rhbFGF21 is performed on the infarction animal model after myocardial infarction, so that the occurrence rate of chronic-stage arrhythmia after myocardial infarction can be obviously reduced; preventive administration of the rhbFGF21 is performed on the infarction animal model before myocardial infarction and one-week continuous intraperitoneal injection administration of the rhbFGF21 is performed on the infarction animal model after myocardial infarction, and complications of myocardial fibrosis and heart failure after myocardial infarction can be obviously prevented. The invention provides a safe and effective treatment method and medicament for preventing and treating ischemic arrhythmia, and also provides a convincing theoretical basis for the rhbFGF21 serving as a medicament for preventing and treating ischemic arrhythmia.

Description

technical field [0001] The present invention relates to a new application of recombinant human fibroblast growth factor-21, in particular to the application of recombinant human fibroblast growth factor-21 in preventing and treating ischemic arrhythmia. The invention belongs to the technical field of biomedicine. Background technique [0002] Globally, 17 million people die from cardiovascular diseases every year, and more than half of them die from myocardial infarction. The number of people dying of myocardial infarction and its complications in my country has exceeded 1 million every year. With the development of thrombolysis and coronary intervention technology, the survival rate of patients with acute myocardial infarction (AMI) has been significantly improved, but there is still a high incidence of ventricular arrhythmia after the acute onset of myocardial infarction, which has become a major cause of myocardial infarction. main cause of death in patients. Myocardia...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61P9/06A61P9/04A61P9/00
CPCA61K38/1825
Inventor 杨宝峰吕延杰杜智敏李校堃王宁张驰王晓杰惠琦
Owner HARBIN MEDICAL UNIVERSITY
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