Drago F, Montoneri C, Varga C, Làszlò F
Institute of Pharmacology, University of Catania Medical School, Italy.
Life Sci. 1999;64(25):2341-50. doi: 10.1016/s0024-3205(99)00187-3.
Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17beta-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200-220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin, and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17beta-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation, and increased mucus levels following cysteamine challenge. Administration of progesterone (10-50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17beta-estradiol (1-5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine, and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17beta-estradiol (1-5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10-50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion.
由于胃十二指肠溃疡的性别差异众所周知，且可能与性激素的作用有关，我们研究了雌性甾体激素、孕酮和17β - 雌二醇在半胱胺诱导的雌性Wistar大鼠（200 - 220克）黏膜溃疡中的作用。通过平面测量法评估，给予半胱胺（400毫克/千克，皮下注射）会引发胃十二指肠黏膜的宏观损伤；通过放射性标记白蛋白外渗评估，胃和十二指肠的微血管通透性增加；通过阿尔新蓝技术评估，胃十二指肠黏液水平降低。卵巢切除术（在给予半胱胺前2周）通过放射免疫测定法评估可降低血浆17β - 雌二醇水平，减少胃十二指肠宏观损伤和白蛋白外渗，并在半胱胺激发后增加黏液水平。给予孕酮（10 - 50毫克/千克/周，皮下注射）以剂量依赖方式减轻半胱胺诱导的胃十二指肠黏膜损伤和微血管渗漏，同时增加胃和十二指肠的黏液水平。相比之下，给予17β - 雌二醇（1 - 5毫克/千克/周，皮下注射）会剂量依赖性地加重半胱胺引发的胃和十二指肠宏观黏膜损伤及微血管损伤，并导致半胱胺给药后观察到的胃十二指肠黏液水平进一步降低。在不同实验中，卵巢切除术可减轻吲哚美辛诱导的胃十二指肠损伤。注射17β - 雌二醇（1 - 5毫克/千克/周）不影响胃十二指肠损伤，而用孕酮（10 - 50毫克/千克/周）治疗可预防吲哚美辛引发的黏膜溃疡。结论是，雌性甾体激素通过调节微血管通透性和黏液分泌在药物诱导的胃十二指肠溃疡中发挥作用。
