Use of mpges-2 as a target in the development or screening or preparation of drugs for the prevention and/or treatment of diseases of aging

An aging and drug technology, applied in the field of biomedicine, can solve the problem of unclear mechanism of mPGES-2 regulating aging, and achieve the effects of improving exercise ability, promoting proliferation and cell rejuvenation

Active Publication Date: 2022-06-24
XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether mPGES-2 plays a regulatory role in aging and its mechanism of regulating aging is still unclear.

Method used

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  • Use of mpges-2 as a target in the development or screening or preparation of drugs for the prevention and/or treatment of diseases of aging
  • Use of mpges-2 as a target in the development or screening or preparation of drugs for the prevention and/or treatment of diseases of aging
  • Use of mpges-2 as a target in the development or screening or preparation of drugs for the prevention and/or treatment of diseases of aging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Doxorubicin-induced aging mouse model

[0046] MPGES-2 WT and KO mice were selected and divided into cages, and the day of the scoring cage was D0. On D1 and D7, intraperitoneal injection of doxorubicin 10 mg / kg body weight was performed to construct an aging model, and the body weight on the day was recorded. D8 is for rotarod fatigue meter adaptation, and D10 is for measurement.

Embodiment 2

[0047] Example 2 Rota-Rod:

[0048] The motor coordination ability of the mice was evaluated by a rotarod fatigue apparatus. The mouse was placed on the roller of the rotarod fatigue apparatus, and its tail was gently pulled to adjust to the rotarod, maintaining a balance movement. After three days of acclimatization, take the test. Rotor speed setting: 30r / min, acceleration from 1r / min to 30r / min, acceleration time 150s, test time 5min. Three rounds of testing were performed, and the average value was taken, with an interval of 10 min between each test. The mouse drop time was recorded.

Embodiment 3

[0049] Example 3 Isolation and culture of MEF cells:

[0050] The 13.5-day pregnant female mice were sacrificed by cervical dislocation, the abdomen was sterilized with alcohol, the abdominal cavity and uterus were opened aseptically, placed in a plate (PBS was added in advance), the fetal membranes were removed, and the fetus was removed (washed with PBS 3-4 times to remove blood cells)

[0051] The limbs, head, tail and internal organs of mouse embryos were removed with ophthalmic scissors, and washed 2-3 times with PBS. After rinsing, use ophthalmic scissors to cut into small tissue pieces of 1 mm.

[0052] For cell digestion and culture, add 4ml of 0.25% trypsin-EDTA, place at 37°C for digestion for 10-15min, and repeatedly pipet with a gun at 5min intervals until no obvious tissue blocks are visible. Digestion was terminated by adding an equal volume of DMEM (10% FBS). Transfer the cell suspension into a centrifuge tube, centrifuge at 1000 rpm for 5 min, and remove the ...

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Abstract

The invention discloses the application of mPGES‑2 as a drug target for preventing and / or treating aging diseases. The present invention proposes for the first time that mPGES‑2 is a drug target for doxorubicin and hydrogen peroxide-induced senescence. Experiments have shown that mPGES‑2 knockout can significantly prolong the lifespan of doxorubicin-induced aging mice and significantly enhance the exercise capacity of doxorubicin-induced aging mice. At the same time, knockout of mPGES‑2 can significantly inhibit hydrogen peroxide-induced aging of primary mouse fibroblast MEFs and promote proliferation. These results indicate that knocking out mPGES‑2 can improve the senescence phenotype induced by doxorubicin, delay the natural aging of MEFs and the accelerated aging induced by hydrogen peroxide, and indicate that mPGES‑2 can be used as a preventive and / or therapeutic agent for doxorubicin and / or The targets of hydrogen peroxide-induced aging and aging-related diseases are of great significance for the development of drugs and the prevention and / or treatment of such diseases in the future.

Description

technical field [0001] The invention specifically relates to the application of mPGES-2 (microsomal prostaglandin E synthase-2) as a drug target for treating and / or preventing aging and aging-related diseases, and belongs to the technical field of biomedicine. Background technique [0002] Aging is a progressive, systemic, multifaceted and very complex degeneration process that occurs in the later stages of life. According to "Nature" magazine, by 2025, the number of people over 60 years old in the world will exceed 1.2 billion, and by 2050, the number of people over 60 years old in my country will exceed 30%, and society will enter a stage of deep aging. And along with aging will also bring a series of disease problems, more than 70% of people over 65 years old suffer from two or more chronic diseases, such as arthritis, diabetes, cancer, heart disease and stroke, and aging has been become the primary risk factor for these chronic diseases. [0003] mPGES-2 is a special b...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N9/90A61K45/00A61P39/06
CPCC12N9/90C12Y503/99003A61K45/00A61P39/06
Inventor 钟丹丹陈京硕孙莹
Owner XUZHOU MEDICAL UNIV
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