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.
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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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