Application of Metrnl in atherosclerosis (AS) resistance

A kind of atherosclerosis, agonist technology, applied in the field of medicine

Pending Publication Date: 2020-01-17
THE NAVAL MEDICAL UNIV OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Application of Metrnl in atherosclerosis (AS) resistance
  • Application of Metrnl in atherosclerosis (AS) resistance
  • Application of Metrnl in atherosclerosis (AS) resistance

Examples

Experimental program
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Embodiment approach

[0033] In addition, the Metrn1 protein can also be artificially prepared, such as prepared according to conventional genetic engineering techniques. Any suitable Metrnl protein is suitable for use in the present invention. The Metrn1 protein includes a full-length Metrn1 protein or a biologically active fragment thereof. As a specific embodiment, the Metrn1 protein may be a human Metrn1 protein with a size of about 30 kDa, and the amino acid sequence is shown in NP_001004431.1.

[0034]The amino acid sequence of Metrn1 protein formed by substitution, deletion or addition of one or more amino acid residues is also included in the present invention. The Metrn1 protein or its biologically active fragment includes a part of conservative amino acid substitution sequence, and the amino acid substitution sequence does not affect its activity or retains its partial activity. Appropriate substitution of amino acids is well known in the art and can be readily performed without alterin...

Embodiment 1

[0039] Embodiment 1: Construction of Metrnl genetically engineered mouse atherosclerosis model

[0040] 1.1 Metrnl - / - ApoE - / - Construction of atherosclerosis model in double knockout mice

[0041] (1) Metrnl systemic knockout mice (Metrnl - / - ) breeding and genotyping

[0042] Metrnl systemic knockout mice (abbreviated as Metrnl - / - ) using the Cre-LoxP gene knockout system (Diabetes2015; 64:4011-4022), according to figure 1 A breeding process is obtained by mating and breeding. where Metrnl loxP / loxP From our unit, Ella-Cre mice were purchased from Shanghai South Model Biotechnology Development Co., Ltd., and C57BL / 6J mice were purchased from Shanghai Xipuer-Bikay Experimental Animal Co., Ltd. Genotype identification method: Ella-Cre gene and Metrnl gene need to be identified. The upstream and downstream primers of the corresponding genes were used to identify the genotype of the mouse tail, and a 100bp band appeared in the positive Ella-Cre gene; the amplified prod...

Embodiment 2

[0054] Example 2: Experimental methods and results of Metrnl anti-atherosclerosis

[0055] 2.1 Experimental method

[0056] (1) Separation of mouse heart and aorta

[0057] Mice were anesthetized by intraperitoneal injection of 1% sodium pentobarbital (100mg / kg), and the chest and abdomen were wiped wet with alcohol cotton balls, and the abdominal cavity and thorax were cut open from the lower part of the manubrium sternum to fully expose the heart and its bottom veins. The syringe draws blood from the vena cava, then cuts a small opening in the right atrium of the heart, fills the 10mL syringe with pre-cooled 1×PBS buffer, inserts the needle tip into the left ventricle of the heart, and slowly pushes in the PBS buffer for perfusion. Afterwards, the lungs, liver, stomach, spleen, pancreas, intestines, fat and reproductive organs were cut off, and the heart, aorta and both kidneys were kept, and the aorta was separated under a microscope. Be careful not to injure the aorta du...

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Abstract

The invention relates to novel application of Metrnl, belongs to the technical field of medicine and in particular relates to application of the Metrnl in atherosclerosis (AS) resistance. A Metrnl<-/->ApoE<-/-> double-knockout mouse AS model and an EC-Metrnl<-/->ApoE<-/-> mouse AS model are constructed, experiments show that the severity of AS of the two Metrnl knockout mice is higher than that ofcontrol mice, reflected in that aortas of the Metrnl knockout mice havemore atherosclerotic plaques than those of control mice, the area ratio of the atherosclerotic plaques of the aortas of the Metrnl knockout mice is higher than that of control mice, the thickening degree and inflammatory infiltration degree of root atherosclerosis of the aortas of the Metrnl knockout mice are higher than thoseof control mice and the expression level of inflammatory factors of the aortas of the Metrnl knockout mice is increased. The invention proves that the Metrnl can be applied to AS resistance by experimentsfor the first time.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of Metrn1 in anti-atherosclerosis. Background technique [0002] Atherosclerosis (AS), as the common pathological basis of cardiovascular and cerebrovascular diseases, has long been one of the focuses and hotspots in the field of cardiovascular disease research, and AS is also the main cause of cardiovascular disease disability and death. Therefore, how to prevent and treat AS is very important for the treatment of patients with cardiovascular disease and the improvement of long-term prognosis. [0003] Metrnl, also known as Subfatin, Cometin, and Interleukin39, is a new type of adipokine discovered by our laboratory (Miao Chaoyu’s research group) in recent years. It is highly expressed in subcutaneous adipose tissue and intestinal epithelial tissue, and is a homologous protein with Meteorin, but Expression distribution and function are quite different. At pres...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61P9/10
CPCA61K38/1709A61K45/00A61P9/10A61K38/17G01N33/68
Inventor 缪朝玉郑斯莉缪玉恩
Owner THE NAVAL MEDICAL UNIV OF PLA
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