钠‑葡萄糖共转运蛋白2抑制剂缓解 精母细胞氧化应激改善2型糖尿病 小鼠生精功能的研究.

Objective To investigate the effect of sodium‑glucose co‑transporter 2 inhibitor (SGLT2i) on spermatogenesis and the quality of sperm in the mice with type 2 diabetes mellitus (T2DM). Methods Twenty‑one 8‑week‑old male db/db mice were randomized into three groups (seven mice in each group) using a random number table method: db/db group (received vehicle), Dapa group [received dapagliflozin (1 mg·kg-1 ·d-1 ) ], and Cana group [received canagliflozin (10 mg·kg-1 ·d-1 ) ], orally daily for five weeks. Five littermate db/m mice were chosen as the normal control group. Body weight and the blood glucose levels were monitored in all mice. Sperm concentration and motility were analyzed using a computer‑assisted semen analysis system. Testicular morphology was evaluated using HE staining, and testicular cell apoptosis was examined using terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) and immunohistochemistry staining. GC‑2 spermatogonia cells, were divided into three groups: normal control (vehicle), PA group (100 μmol/L palmitic acid intervention), and PA+Dapa group (100 μmol/L palmitic acid combined with 30 μmol/L dapagliflozin intervention) and treated for 48 h. Oxidative stress levels and apoptosis‑related indices were assessed using Western blotting, flow cytometry and test kits. One‑way analysis of variance or Brown‑Forsythe/Welch was used to compare between groups. Results Compared with db/db mice, dapagliflozin and canagliflozin significantly reduced fasting and postprandial blood glucose levels and the area under the glucose curve (all P<0.05). Both interventions increased sperm viability and progressive motility, as well as curve velocity and mean path velocity (all P<0.05). They also decreased activated caspase‑3 expression, TUNEL‑positive spermatogenic tubule ratio, and cell ratio (all P<0.05). In GC‑2 cells, intervention with dapagliflozin reduced intracellular reactive oxygen species levels, malondialdehyde content, increased superoxide dismutase activity, decreased apoptosis rate, and increased B‑cell lymphoma 2 (BCL2) expression (all P<0.05) compared with the PA group. Conclusion SGLT2i provide additional protective effects on testicular structure and sperm quality in db/db mice with T2DM in addition to their hypoglycemic effects. SGLT2i may protect against diabetes‑induced spermatogenesis impairment by attenuating testicular oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]