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Application of mPGES-2 as drug target for preventing and/or treating aging diseases

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 effect of improving exercise ability, rejuvenating cells, and delaying natural aging.

Active Publication Date: 2022-03-01
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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  • Application of mPGES-2 as drug target for preventing and/or treating aging diseases
  • Application of mPGES-2 as drug target for preventing and/or treating aging diseases
  • Application of mPGES-2 as drug target for preventing and/or treating aging diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Aging mouse model induced by doxorubicin

[0047] Select mPGES-2WT and KO mice, divide them into cages, and score the cage day as D0. On D1 and D7, intraperitoneal injection of doxorubicin 10 mg / kg body weight was carried out to establish the aging model, and the body weight of the day was recorded. D8 is adapted to the rotary rod fatigue tester, and D10 is used for measurement.

Embodiment 2

[0048] Example 2 Rota-Rod:

[0049] The motor coordination ability of the mice was assessed using a rotarod fatigue tester. Put the mouse on the roller of the rotating rod fatigue instrument, gently pull its tail to make it adapt to the rotating rod, and maintain a balanced movement. After three days of acclimatization, the test was carried out. Rod speed setting: 30r / min, acceleration from 1r / min to 30r / min, acceleration time 150s, test time 5min. Test three rounds, take the average value, and the interval between each test is 10min. Record the mouse drop time.

Embodiment 3

[0050] The separation and cultivation of embodiment 3 MEF cells:

[0051] Take the 13.5-day pregnant female mouse, kill it by neck breaking, disinfect the abdomen with alcohol, open the abdominal cavity and uterus aseptically, put it on a plate (add PBS in advance), remove the fetal membrane, and take out the fetus (wash 3-4 times with PBS to remove blood cells)

[0052] Use ophthalmic scissors to remove limbs, head, tail and viscera of mouse embryos, and wash with PBS 2-3 times. After washing, cut into small tissue pieces of 1 mm with ophthalmic scissors.

[0053] Add 4ml of 0.25% trypsin-EDTA to cell digestion and culture, put it at 37°C for 10-15min, and repeatedly pipette with a gun at intervals of 5min until no obvious tissue blocks can be seen. Digestion was terminated by adding an equal volume of DMEM (10% FBS). Transfer the cell suspension into a centrifuge tube, centrifuge at 1000rpm for 5min, and remove the supernatant. Suspend cells in 1-2ml of DMEM (10% FBS). 3...

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Abstract

The invention discloses an application of mPGES-2 as a drug target for preventing and / or treating aging diseases. The invention proposes that mPGES-2 is a doxorubicin and hydrogen peroxide induced senescence drug target for the first time. Experiments show that mPGES-2 knockout can significantly prolong the life of adriamycin-induced senescent mice and significantly enhance the athletic ability of the adriamycin-induced senescent mice. Meanwhile, mPGES-2 knockout can obviously inhibit senescence, caused by hydrogen peroxide, of primary mouse fibroblast MEF, and proliferation is promoted. The results show that the doxorubicin-induced senescence phenotype can be improved and the natural senescence of MEF and the accelerated senescence caused by hydrogen peroxide can be delayed by knocking out the mPGES-2, so that the mPGES-2 can be used as a target for preventing and / or treating doxorubicin and / or hydrogen peroxide-induced senescence and senescence-related diseases thereof; and the compound has very important significance on drug development and prevention and / or treatment of the 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, complex [0003] the degradation process. According to the "Nature" magazine, by 2025, the number of people over 60 years old worldwide 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 aging will also bring a series of disease problems, more than 70% of people over the age of 65 suffer from two or more chronic diseases, such as arthritis, diabetes, cancer, heart disease and stroke, and aging has already become the leading risk factor for these chronic diseases. [0004] mPGES-2 is a special bidirectional enzyme, mPGES-2 combines wit...

Claims

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Application Information

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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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