Application of TRPV4 agonist in preparation of medicine for treating and/or preventing male infertility

A male infertility, agonist technology, applied in drug combinations, sexual diseases, pharmaceutical formulations, etc., can solve problems such as unreported, decreased sperm motility, etc.

Active Publication Date: 2022-06-03
NANHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there are no reports of GSK1016790A treating and relieving diabetes-induced oligospermia, decreased sperm motility, and sperm deformity, and there is no relevant research on the treatment of male infertility based on this

Method used

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  • Application of TRPV4 agonist in preparation of medicine for treating and/or preventing male infertility
  • Application of TRPV4 agonist in preparation of medicine for treating and/or preventing male infertility
  • Application of TRPV4 agonist in preparation of medicine for treating and/or preventing male infertility

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 Investigate the effect of TRPV4 agonist GSK1016790A on spermatogenesis in STZ-induced diabetic mice

[0026] Animals: 36 male ICR male mice, 3 months old, weighing about 30-40 g. Animals were kept at room temperature (22±2)°C, humidity (45%-65%) and alternating light and dark (12h:12h), with free access to food and water. Animal grouping and treatment Mice were divided into 3 groups according to random number table method: vehicle control group (NS+DMSO, n=12), diabetic spermatogenesis disorder model group (STZ+DMSO, n=12), GSK1016790A group (STZ+GSK , n=12), the mice were given intraperitoneal injection of streptozotocin (STZ, 55 mg / kg) after fasting for 6 h every day (8:30-14:30) for five consecutive days to establish a diabetic mouse model. Mice in the NS+DMSO group were injected with an equal volume of normal saline in the same way. GSK1016790A (0.125mg / kg) or its vehicle DMSO was injected intraperitoneally for 7 days on the 50th-56th day after the last ...

example 2

[0032] Example 2 Testicular histomorphological detection

[0033] Take the testis and put it in 4% paraformaldehyde solution for more than 24h. Dehydrated with graded ethanol, cleared with xylene, and immersed in wax to prepare for embedding. The tissue soaked in wax was embedded in an embedding machine, cooled in a -20°C refrigerator, and sliced ​​with a thickness of 5 μm after the wax block was solidified. Sections were stained with hematoxylin for 3-8 min, rinsed with running water, differentiated with 1% hydrochloric acid and ethanol for several seconds, rinsed with running water, returned to blue with 0.6% ammonia water, and rinsed with running water. Sections were stained in eosin staining solution for 1-3 min. Dehydrated, mounted, and observed under a microscope. The result is as figure 1 shown:

[0034] Histomorphological results of mouse testis: The spermatogenic cells in the testicular seminiferous tubules of mice in the NS group were neatly arranged, with disti...

example 3

[0035] Example 3 Detection of serum testosterone level by ELISA

[0036]Clinically, the reproductive hormone levels of infertile patients are often detected and used as an important reference for the treatment of infertility, among which testosterone (T) is the most commonly used. Blood was collected from animals in each group, and serum testosterone levels were detected by ELISA. The result is as figure 2 shown.

[0037] Results: Compared with mice in NS group, the serum testosterone content of mice in STZ group was significantly decreased, and the content of serum testosterone in mice treated with GSK1016790A returned to the level of control group. It was shown that GSK1016790A could effectively increase the plasma testosterone content in STZ mice.

[0038] The above results show that the TRPV4 agonist GSK1016790A has a significant protective effect on streptozotocin (Streptozotocin, STZ)-induced spermatogenesis dysfunction in diabetic mice.

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Abstract

The invention relates to the technical field of biological medicines, in particular to application of a TRPV4 agonist in preparation of a medicine for treating and/or preventing male infertility. Experiments show that the TRPV4 agonist (such as GSK1016790A) can improve the sperm number and the sperm motility rate of a spermatogenesis disorder model mouse and reduce the sperm malformation rate of the mouse, so that the TRPV4 agonist is used for preparing the medicine for enhancing the spermatogenesis function of male animals or human beings, provides a new candidate medicine for treating male infertility, and has better economic significance.

Description

technical field [0001] The present invention relates to the field of biotechnology, in particular to the application of a TRPV agonist in preparing a medicine for treating and / or preventing male infertility. Background technique [0002] At present, about 15% of couples of childbearing age in the world cannot conceive within one year of marriage and need interventional treatment, of which male factors account for about 50%. Semen examination in infertile men is mainly characterized by oligospermia, asthenozoospermia or oligoasthenospermia. Decreased semen quality in men can lead to temporary or permanent infertility, or decreased fetal quality, causing enormous mental stress to individuals, great pain to families, and even life tragedies, which has become a social problem that must be paid attention to. In the process of diagnosis and treatment, most patients cannot find a clear cause, and there is still a lack of specific treatment drugs. [0003] Diabetes is a global pub...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/496A61P15/08
CPCA61K31/496A61P15/08Y02A50/30
Inventor 李素云孟星圻彭莉轩徐杨曹文宇
Owner NANHUA UNIV
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