Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
Neurosci Lett. 2013 Jun 28;547:53-8. doi: 10.1016/j.neulet.2013.05.014. Epub 2013 May 14.
Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. The cytoprotective effect of midazolam on brain astrocytes is poorly understood. This study aimed to investigate the cytoprotective effect of midazolam on astrocytes exposed to corticosterone, a stress-produced glucocorticoid. We found that midazolam stimulated pregnenolone and progesterone secretion in astrocytes in a dose-dependent manner. Midazolam protected astrocytes from corticosterone-induced damages in a dose-dependent manner. In addition, we demonstrated that progesterone reduced corticosterone-induced damages. Finally, we applied trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, to inhibit pregnenolone metabolism and found that pretreatment with trilostane significantly inhibited the cytoprotective effect of midazolam on corticosterone-induced cytotoxicity in rat astrocytes in a dose-dependent manner. Taken together, these results demonstrate that midazolam has cytoprotective effect on astrocytes. This is, at least partially, derived from midazolam-induced steroidogenesis including progesterone and downstream products in astrocytes. Our data provide new insights into the cytoprotective effect of midazolam.
咪达唑仑是一种苯二氮䓬类衍生物药物，具有强大的抗焦虑、健忘、催眠和镇静作用。咪达唑仑对脑星形胶质细胞的细胞保护作用知之甚少。本研究旨在探讨咪达唑仑对皮质酮（应激产生的糖皮质激素）作用下星形胶质细胞的细胞保护作用。我们发现咪达唑仑以剂量依赖的方式刺激星形胶质细胞中孕烯醇酮和孕酮的分泌。咪达唑仑以剂量依赖的方式保护星形胶质细胞免受皮质酮诱导的损伤。此外，我们证明孕酮可减少皮质酮诱导的损伤。最后，我们应用 3β-羟甾脱氢酶抑制剂三氯司坦来抑制孕烯醇酮的代谢，发现三氯司坦预处理以剂量依赖的方式显著抑制咪达唑仑对皮质酮诱导的大鼠星形胶质细胞毒性的细胞保护作用。综上所述，这些结果表明咪达唑仑对星形胶质细胞具有细胞保护作用。这至少部分源于咪达唑仑诱导的类固醇生成，包括星形胶质细胞中的孕酮和下游产物。我们的数据为咪达唑仑的细胞保护作用提供了新的见解。
