LGR4 gene/protein for screening medicine for treating hypercholesteremia

A technology for hypercholesterolemia and cholesterol, applied in the fields of biotechnology and medicine, can solve the problems that the specific role of LGR4 has not been deeply explored, and no research has revealed the impact of LGR4, so as to achieve good application prospects, reduce blood cholesterol levels, and reduce low density Effect of lipoprotein cholesterol levels

Active Publication Date: 2017-02-22
SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above related studies have focused on the impact of LGR4 on the development of the body. In recent years, studies have shown its association with energy metabolism. LGR4 knockout mice have significantly reduced body weight, improved glucose tolerance, and can resist high-fat diet-induced obesity and hereditary obesity, revealed the regulatory role of LGR4 on adipose tissue, but did not explore the specific role of LGR4 on other metabolic-related organs
[0004] In recent years, clinical studies have confirmed that low-density lipoprotein cholesterol (LDL-C) is closely related to coronary heart disease. Most of the LDL-c in the blood is cleared by LDL receptors on the surface of the liver. Therefore, blood cholesterol levels are closely related to liver disease. It is closely related to the metabolic function of LGR4, but no research has yet revealed the impact of LGR4 on the liver and its role in liver cholesterol metabolism

Method used

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  • LGR4 gene/protein for screening medicine for treating hypercholesteremia
  • LGR4 gene/protein for screening medicine for treating hypercholesteremia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1. Establishment of adenovirus-mediated liver-specific LGR4 gene knockout mice

[0025] 20 db / db mice were raised in the animal room of the Institute of Endocrinology, School of Medicine, Shanghai Jiaotong University. Body weight calibration, respectively for the control group (Ad-sh-CTRL) and the LGR4 knockout group (Ad-sh-LGR4) two groups. After grouping, the rats were given tail vein injection of adenovirus, the control group was given 2*109pfu shNT adenovirus injection, and the LGR4 knockout group was given 2*109pfu shLGR4 adenovirus injection.

[0026] 24 high-fat mice were raised in the animal room of the Institute of Endocrinology, Shanghai Jiao Tong University School of Medicine. The ambient temperature was 22°C, with 12 hours / 12 hours of light and dark. db / db mice.

Embodiment 2

[0027] Embodiment 2, establish Lgr4; Leptin (Lgr4 m / m ; ob / ob) double-gene mutant mice

[0028] Lgr4 heterozygous mice were backcrossed with C57BL / 6 mice for at least 6 generations to obtain Lgr4 heterozygous mice with C57BL / 6 background. The mice obtained by mating these Lgr4 heterozygous mice with ob mice were designated as F2, and the Lgr4 and Leptin double mutant mice among the offspring obtained by crossing the F2 generation mice were used for the experiment, and the ob mice were used for the control. Three-month-old male and female mice were mated in cages at a ratio of 1:1 and 1:2. Three-week-old mice were weaned, marked, separated into cages, and genotyped.

Embodiment 3

[0030] Feeding conditions: mice were raised under clean-grade conditions, and the feeding density was 5 per cage, and were fed separately in standard mouse cages according to the following conditions: standard commercial mouse feed (4.5% fat, 4.0% cellulose, 21.0% Protein, 1.404 kcal / gram), high-fat feeding feed was purchased from Research Diet (60.0% fat), and the feed was replaced every other day according to the food intake of each mouse to ensure the freshness of the feed. The room temperature was 20-22 degrees Celsius, free access to food and water, and a stable artificial light cycle (6:00 to 18:00 light, 18:00 to 6:00 dark).

[0031] Two kinds of adenovirus injection mouse models were collected 10 days after injection of adenovirus, Lgr4; Leptin(Lgr4 m / m ; ob / ob) The double-gene mutant mouse model was collected at the age of 4 months. The feed of the animals in each group was removed at 17:00 the day before the collection, and the animals were fasted for 16 hours, and a...

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Abstract

The invention discloses an LGR4 gene/protein for screening medicine for treating hypercholesteremia. The LGR4 gene serves as a molecular target or medicine acting target, and is used for screening or preparing the medicine for treating hypercholesteremia and low-density lipoprotein cholesterin. The new application of the glycoprotein hormone receptor LGR4 gene in a G protein-coupled receptor is provided, a new target is provided for treatment on hypercholesteremia and high density lipoprotein and low-density lipoprotein cholesterol (LDL-c) adaptation diseases, and good application prospects are achieved.

Description

technical field [0001] The invention relates to the fields of biotechnology and medicine, and specifically uses LGR4 gene / protein as a drug target to screen drugs for treating hypercholesterolemia. Background technique [0002] According to the latest survey data released by WHO, deaths caused by ischemic heart disease and stroke account for a quarter of the total number of deaths worldwide, and are currently the leading cause of death in most countries. Hypercholesterolemia is an independent risk factor for ischemic cardiovascular disease. When TC ≥ 5.72mmol / L, the risk of acute coronary heart disease increases by 74%. Among ischemic cardiovascular events, 5.9% can be attributed to high Cholesterolemia. Therefore, research on drugs for lowering blood cholesterol levels is particularly important. [0003] LGR4 is a member of the G protein-coupled receptor (GPCR) family, located in the chromosome 11p14 segment, with a total length of about 106Kb, including 18 exons, encodin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/92C12N15/85A61K45/00A61P3/06
CPCA61K45/00C12N15/85C12N2800/107G01N33/92G01N2800/044G01N2800/32
Inventor 宁光张志国王计秋姚霜霜
Owner SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES
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