动物造模 z-bio 2022-06-17 350

　　Objective To investigate the effect and mechanism of androgens on gastric mucosal mitochondrial function in aged rats with orchiectomy (GDX).

　　Methods Thirty-six SD male rats were randomly divided into 3 groups: sham operation group (Sham, n = 12), model group (GDX, n = 12) and model rats supplemented with androgen (n = 12). The model rats were given GDX, and testosterone (13. 6 mg/(kg·d), dissolved in sesame oil) was administered orally in the androgen group after model establishment. Rats in the sham-operated and model groups were treated the same with sesame oil. Gastric tissue samples were collected after treatment, kits were used to detect the levels of Mn-SOD, GSH-Px, GSH, GSSG, GSH/GSSG and ROS in gastric mucosa mitochondria, rhodamine 123 fluorescence method was used to detect mitochondrial membrane potential, and flow cytometry was used to detect mitochondrial membrane potential. Detection of apoptosis. Human immortal gastric mucosal cells GES-1 were used as the research object in the in vitro experiments, and H2O2 was used to induce cell damage, and the effects of androgens and ALDH2 inhibitor Disulfiram on cell viability and apoptosis were investigated.

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

　　Conclusions Androgen deficiency leads to mitochondrial dysfunction and increased accumulation of mitochondrial ROS in gastric mucosal cells in aged rats, and induces gastric mucosal cell apoptosis. This damage is at least partially related to the inhibition of ALDH2 antioxidant function.