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Application of recombinant human fibroblast growth factor 21 in prevention and treatment of atherosclerosis and related diseases

A technology of human fibroblasts and atherosclerosis, which is applied in the application field of proteins in the diagnosis or treatment of diseases related to coronary heart disease. Effect

Inactive Publication Date: 2015-06-03
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, little is known about the relationship between FGF21 and CHD, both in animals and clinically
Disturbance of lipid metabolism is one of the main mechanisms of AS pathogenesis, and hyperglycemia is one of the high risk factors of AS pathogenesis, but whether FGF21 is related to AS pathogenesis and what pathways it uses to regulate the metabolic process in the body need to be further explored

Method used

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  • Application of recombinant human fibroblast growth factor 21 in prevention and treatment of atherosclerosis and related diseases
  • Application of recombinant human fibroblast growth factor 21 in prevention and treatment of atherosclerosis and related diseases
  • Application of recombinant human fibroblast growth factor 21 in prevention and treatment of atherosclerosis and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Recombinant human fibroblast factor 21 prevents atherosclerosis

[0040] 1. Animal grouping and drug treatment arrangement

[0041] Thirty 8-week-old ApoE KO mice were divided into three groups, A / B / C, with 10 mice in each group. In addition, 10 C57BL / 6j mice with the same genetic background were used as the normal control group (Group D) , Groups A / B / C were given high-fat diet, and groups A / B were subcutaneously injected with recombinant FGF21 protein at doses of 100 and 400 μg / kg respectively, and groups C / D were injected with normal saline subcutaneously as a control After two weeks, the mice in the four groups A / B / C / D were uniformly fed with normal feed. During the administration process, the body weight of the mice was detected every 2 weeks to observe the body weight change.

[0042] 2. Animal sacrifice and tissue sample collection

[0043] After 6 weeks of administration, the mice were sacrificed, the mice were fasted overnight, anesthetized with ethe...

Embodiment 2

[0134] Clinical manifestations of embodiment 2FGF21 in patients with coronary heart disease

[0135] 1. CHD clinical case collection and clinical analysis methods

[0136] (1) Clinical diagnostic criteria

[0137] According to the "nomenclature and diagnostic criteria for ischemic heart disease" issued by the World Health Organization (WHO) in 1999 and the current clinical diagnostic criteria for CHD in my country, patients with coronary heart disease with angina pectoris or myocardial infarction were listed as the research objects. The specific diagnostic criteria are as follows: ①The clinical diagnosis of myocardial infarction is based on the patient’s ECG test results, elevated serum enzymes in serological tests, and clinical symptoms such as chest discomfort. ②Angina pectoris is based on the following clinical manifestations and detection indicators as the diagnostic criteria, that is, the main manifestation is frequent emotional excitement or chest discomfort for 15 minu...

Embodiment 3

[0157] Embodiment 3 The expression of FGF21 in the mouse model of atherosclerosis

[0158] 1. Grouping of animals

[0159] 20 8-week-old apoE -／- Male mice were randomly divided into two groups A / B, 10 in each group. Group A was fed with high-fat diet, and group B was fed with normal diet. At the same time, 10 normal C57 / BL6j mice were taken as the experimental control group (group C), and fed with normal diet.

[0160] 2. Collection of mouse blood samples

[0161] Before the start of the animal experiment, the above two groups A / B were fasted overnight, blood was collected from the fundus vein, the serum was separated, stored in a -80°C refrigerator, and used as the serum FGF21 test specimen of 8-week-old mice; then at 12 and 24 weeks respectively Blood samples were collected at age, and the changes of serum FGF21 circulating levels were observed.

[0162] 3. Animal sacrifice and tissue sample collection

[0163] When the animals in each group reached the age of 24 weeks...

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Abstract

The invention discloses a genetic engineering protein-recombinant human fibroblast growth factor 21 capable of preventing and treating atherosclerosis and related diseases. The recombinant human FGF21 protein obtains patent protection by an applicant (the potential number: ZL200810223501.0). The recombinant human FGF21 protein is capable of effectively relieving and controlling pathogenesis of atherosclerosis by promoting external flow of fat in vascular endothelial cells and reducing accumulation of fat in blood vessel endothelium. Therefore, compared with other listed medicines, the recombinant human FGF21 protein has the advantage that prevention and treatment can be carried out with respect to the sources of atherosclerosis and a coronary heart disease. In addition, through analysis of a lot of clinical data, the inventor discovers that the FGF21 can be applied to auxiliary diagnosis of indexes of the atherosclerosis and the coronary heart disease, and has remarkable correlation in content increase in serum and morbidity of the coronary heart disease. In view of wide action of the recombinant human FGF21 protein in prevention, treatment and diagnosis of the atherosclerosis, the inventor believes that the clinical application value of the recombinant human fibroblast growth factor 21 is great.

Description

technical field [0001] The invention relates to a protein with pharmacological effects, in particular to the application of a protein in diagnosing or treating diseases related to coronary heart disease. Background technique [0002] Atherosclerosis (AS) is an important pathological basis of cardiovascular and cerebrovascular diseases, and is also an important hub of metabolic syndrome. Arterial wall thickening, loss of elasticity and lumen narrowing are the common characteristics of various AS. Epidemiological and clinical studies have shown that AS mainly occurs in middle-aged and elderly people over the age of 40, and progresses rapidly after the age of 49. However, early atherosclerosis has also been found in the arteries of some young adults and even children in autopsies sclerotic lesions. Coronary atherosclerotic heart disease refers to the heart disease caused by coronary atherosclerosis narrowing or blocking the vascular lumen, or myocardial ischemia, hypoxia or ne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P9/10G01N33/68
Inventor 李校堃林灼锋潘薛波吴帆金雷钢
Owner WENZHOU MEDICAL UNIV
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