A. Glucocorticoid d uas Iru Mechanisms of glucocorticoid actions binding to glucocorticoid receptor (Gr) nuclear translocation binding to GR element r regulating retated gene transcription o bIological elects (usually Slow)
§ Mechanisms of glucocorticoid actions A. Glucocorticoid drugs
CBG CBG s Action mode of glucocorticoid drugs GR S(HSP70 CBG: corticosteroid binding HSP70 GR globulin (HSP90) HSP90) S: glucocorticoid steroids nucleus GR: glucocorticoid receptor Transcription GRGR HSP: heat shock protein GREGRE「■口 IP: immunophilin gene GRE: glucocorticoid- mRNA response element cytoplasm protein Altered cellular function
细胞质 B.糖皮质激素 细胞质 核 AP-1 AP-1 受体 炎喻长 0 热休克蛋白 NF-kB/I-kB 炎症信号 其他因子 炎症基因表达 NF-KB/I-kB Ⅰ-KB表达 (降解) I-kB Examples of glucocorticoid actions Inhibition of proinflammatory gene transcription(AP-1 and NFxB)
A. Glucocorticoid d uas Iru (1) Effects on metabolisms a)Carbohydrate: blood glucose t: gluconeogenesis t, ucose utilization↓ b)Protein: synthesis degradation c)Lipid: plasma cholesterol t, fat redistribution(central obesity: moon face, buffalo hump) d) Water and electrolytic: Na* excretion l K+ excretion t, Ca2+ excretiontand absorption
A. Glucocorticoid drugs
A. Glucocorticoid d Iru uas (2)Permissive action Potentiating the effects of catecholamines and glucagon (3)Anti-inflammatory effects Acute: inhibiting microvascular leakage leukocyte infiltration Chronic: inhibiting fibroblast proliferation deposition of collagen cicatrization(癜痕形成)
A. Glucocorticoid drugs