动物造模 z-bio 2022-12-13 308

　　Objective To investigate the effect of androgen on mitochondrial function of gastric mucosa in aged rats with testicular resection (GDX) and its mechanism.

　　Methods Thirty six male SD rats were randomly divided into three groups: sham operation group (Sham, n=12), model group (GDX, n=12) and androgen supplemented model rats (n=12). The model rats were given GDX. After the model was established, testosterone (13.6 mg/(kg · d), dissolved in sesame oil) was administered orally to the androgen group. The rats in sham operation group and model group were treated with sesame oil in the same way. After the treatment, gastric tissue samples were collected, and the levels of Mn SOD, GSH Px, GSH, GSSG, GSH/GSSG and ROS in gastric mucosal mitochondria were detected by kit respectively. Mitochondrial membrane potential was detected by rhodamine 123 fluorescence method, and apoptosis was detected by flow cytometry. In vitro, human immortalized gastric mucosal cell line GES-1 was used as the research object. H2O2 was used to induce cell damage, and the effects of androgen and ALDH2 inhibitor Disulfire on cell viability and apoptosis were investigated.

　　Results Compared with Sham group, the levels of ROS, GSSG, caspase-3 of gastric mucosal cell apoptosis and lysis, and the expression of cytoplasmic Cyt c protein were significantly increased in GDX group (P<0.05), while the levels of Mn SOD, GSH Px, GSH, GSH/GSSG, mitochondrial membrane potential, ATP level, and the expression of mitochondrial Cyt c protein, ALDH2 protein were significantly decreased in GDX group (P<0.05). After androgen treatment, the above changes in GDX aged rats were significantly reversed (P<0.05). In vitro, androgen treatment significantly reversed the damage of H2O2 on GES-1 cells (P<0.05); However, when Disulfaram was added in combination, the therapeutic activity of androgen was significantly reduced (P<0.05).

　　Conclusion Androgen deficiency can lead to mitochondrial dysfunction and increase the accumulation of mitochondrial ROS in gastric mucosal cells of aged rats, and induce apoptosis of gastric mucosal cells. This damage is at least partially related to the inhibition of the antioxidant function of ALDH2.