L-carnitine Reduces Testicular Damage In Rats Under Simulated High Altitude By Affecting PI3K/Akt/HIF-1α Pathway

Objective: The reproductive system injury model of male rats in a simulated high altitude environment through a low pressure and hypoxic animal cabin was to observe the effects of low pressure and hypoxic environment and the intervention of L-carnitine on the morphology of rat testis,compare the differences on the expression of PI3 K,Akt,HIF-1α protein and m RNA in rat testis tissues between groups.To explore whether L-carnitine exerts preventive and protective effects by affecting the PI3K/Akt/HIF-1α pathway.Methods: 60 Wistar rats with a well-developed SPF reproductive system were divided into 4groups: normal control group,hypobaric hypoxia group,hypobaric hypoxia normal saline group,hypobaric hypoxia L-carnitine group.Except for the normal control group,the remaining 3 groups were placed in a hypobaric oxygen chamber,and the simulated altitude was set to 6000 m.Levocarnitine was administered by intraperitoneal injection at a dose of100 mg/Kg,and physiological saline was injected at the same volume once a day for 14 days.The rats were sacrificed after the expiration of the administration period,and the pathological changes of testicular tissues in each group were observed by HE staining.The protein expression levels of PI3 K,AKT,and HIF-1α in the testis tissues of rats in each group were determined by immunohistochemistry and western blotting.Fluorescence quantitative PCR method was used to detect the m RNA levels of PI3 K,AKT,and HIF-1α in rat testis.Results: There was no obvious abnormality in the testis morphology of rats in the normal control group.The testis morphology of the rats in the hypoxic hypoxia group and the hypobaric hypoxia saline group was significantly damaged.The number of cell layers in the lumen of the seminiferous tubules was reduced,and vacuolation and spermatogenesis were observed.Compared with the hypobaric hypoxia saline group,the number of cells in the lumen of the seminiferous tubules in the testis tissue of the rats in the hypobaric hypoxia L-carnitine group was significantly improved,the vacuole area was also significantly reduced.Compared with the normal control group,the expression levels of PI3 K,AKT,and HIF-1αprotein in the testis of the hypobaric hypoxia group,hypobaric hypoxia saline group,and hypobaric hypoxia L-carnitine group were significantly increased(P<0.05 or P<0.01).Compared with the hypobaric hypoxia normal saline group,the expression levels of PI3 K,AKT,and HIF-1α protein in the testis tissue of the hypobaric hypoxia L-carnitine group were significantly increased(P<0.05 or P<0.01).Compared with the normal control group,the levels of PI3 K,AKT,and HIF-1α m RNA in the testis of the hypobaric hypoxia group,hypobaric hypoxia saline group,and hypobaric hypoxia L-carnitine group were significantly increased(P<0.01).Compared with the hypobaric hypoxia normal saline group,the levels of PI3 K,AKT,and HIF-1α m RNA in the testis tissue of the hypobaric hypoxia L-carnitine group increased significantly(P<0.01).Conclusion:1.Levocarnitine intervention can significantly improve the pathological morphology of rat testis under low pressure and hypoxia environment.2.Levocarnitine intervention can up-regulate the expression levels of PI3 K,AKT,HIF-1αprotein and m RNA in rat testis tissue under low pressure and hypoxia environment.