应激性胃溃疡与孕酮的保护作用及其机制

Protective effect and mechanism of progesterone on stress gastric ulcers

目的:观察不同剂量和不同作用时间孕酮对应激性胃溃疡的预防和治疗作用。方法:实验于2005-02/06在山东师范大学生理实验室完成。选择健康昆明种雄性小鼠100只,鼠龄4～6周,体质量22～24g。建立束缚冷水应激性胃溃疡模型,按照实验要求进行小鼠分组。①孕酮对应激性胃溃疡的保护作用:小鼠分为4组,即对照组和0.4mg/kg,0.8mg/kg,1.6mg/kg孕酮注射组,每组10只。对照组在应激前0.5h肌肉注射生理盐水0.5mL,孕酮注射各剂量组分别在应激前0.5h肌肉注射0.4mg/kg、0.8mg/kg、1.6mg/kg孕酮,应激3h后计算胃溃疡指数及测定胃液pH值。②孕酮对应激性胃溃疡的治疗作用:小鼠分为5组,即应激后即刻组,生理盐水5h组,生理盐水7h组,孕酮5h组,孕酮7h组,每组10只。应激后即刻组于应激后即刻注射生理盐水0.5mL;生理盐水5h,7h组应激后注射生理盐水0.5mL分别恢复5,7h后计算胃溃疡指数。孕酮5h,7h组在应激后注射孕酮0.8mg/kg分别恢复5,7h后计算胃溃疡指数。并制备小鼠离体小肠,置于灌流槽,记录不同浓度的孕酮(5,50,100μmol/L)对小肠平滑肌收缩的影响。结果:实验过程中无动物意外死亡、丢失及补充,100只小鼠均进入结果分析。①与对照组相比,各孕酮注射组(0.4,0.6,0.8mg/kg)的溃疡指数都明显降低,且表现随孕酮浓度的增加抑制效果越明显[(40.91±23.30),(12.42±11.80),(12.64±8.86),(6.67±4.81)]。但各孕酮注射组的胃液pH值与对照组相比无明显变化。表明孕酮对应激性胃溃疡有明显预防保护作用,但对胃酸的分泌无影响。②小鼠束缚加冷水应激后3h即刻测得溃疡指数为(39.6±20.8),与即刻组相比,应激后注射生理盐水恢复5h、7h溃疡指数降低且7h后降低较明显[(27.6±17.5),(22.1±15.5)]。表明离开应激环境,小鼠胃粘膜有自我修复能力。应激后注射孕酮恢复5h溃疡指数为(19.1±10.5),注射孕酮恢复7h溃疡指数为(11.9±9.7),与应激性即刻相比胃溃疡指数明显减少。注射孕酮后7h的溃疡指数与注射生理盐水7h相比,溃疡指数明显减少。③正常对照组离体小肠收缩频率为(50.0±9.5)次/min,幅度为(3.24±1.3)mm,而向浴槽中滴加5,50,100μmol/L孕酮后,与对照组相比,孕酮各组的离体小肠的收缩频率和幅度明显降低,且呈现浓度依赖性[(37.7±11.7)次/min,(2.78±1.1)mm];[(34.08±2.6)次/min,(2.65±0.4)mm];[(25.13±2.4)次/min,(2.67±0.9)mm],孕酮能抑制离体小肠的收缩。结论:孕酮对应激性胃溃疡有保护作用,其机制可能与孕酮抑制胃肠平滑肌的收缩有关,而与胃酸的分泌无关。

AIM： To observe the preventive and therapeutic effects of progesterone of different dosages and different action times on stress gastric ulcers. METHODS： The experiment was conducted in the physiological laboratory of Shandong Normal University from February to June 2005. Totally 100 healthy 476-week-old Kunming mice of 22-24 g were randomly divided into groups after made into models of stress gastric ulcers by restrain and put into cold water. （1） Protective role of progesterone in gastric ulcers： The mice were divided into 4 groups with 10 mice in each group, namely, control group and groups injected with 0.4, 0.8 and 1.6 mg/kg progesterone respectively. At 30 minutes before the stress, mice in the normal saline group were injected with 0.5 mL saline, and those in the progesterone injected groups were injected with 0.4, 0.8 and 1.6 mg/kg progesterone respectively. The uleeration index was calculated and the pH value of gastric juice was measured at 30 minutes after the onset of stress. （2） Therapeutic role of progesterone in gastric ulcers： The mice were divided into 5 groups with 10 mice in each group： 0-hour stress group, 5 and 7-hour saline groups, 5 and 7-hour progesterone groups. Mice in the 0-hour stress group were injected with 0.5 mL saline immediately after stress; those in the 5 and 7-hour saline groups were injected with 0.5 mL saline after stress, and the ulceration index was calculated at 5 and 7 hours after recovery respectively; and those in the 5 and 7-hour progesterone groups were injected with 0.8 mg/kg progesterone after stress, and the ulceration index was calculated at 5 and 7 hours after recovery respectively. The isolated mice duodenal smooth muscle were prepared and placed in the perfusiou chamber, and the effects of progesterone of different concentrations （5, 50, 100 μmol/L） on the contractility of duodenal smooth muscle were recorded. RESULTS： All the 100 mice were involved in the analysis of results. （1） As compared with the control group, the ulceration indexes in the progesterone injected groups （0.4, 0.6, 0.8 mg/kg） were all obviously decreased, and the inhibitive effects became more obvious with the increase of progesterone conCentration [（40.91±23.30）, （12.42±11.80）, （12.64±8.86）, （6.67 ±4.81）], but the pH value of gastric juice had no obvious changes in the progesterone injected groups. It was suggested that progesterone had obvious preventive and therapeutic effects on stress gastric ulcers and had no influence on the secretion of gastric acid. （2） The ulceration index at 3 hours after the stress of cold water 2was 39.6±20.8, it was decreased in the 5 and 7-hour saline groups, which was more obviously in the 7-hour saline group as compared with the 0-hour stress group [（27.6±17.5）, （22.1±15.5）], indicating that the gastric mucosa of mice had the self-repair ability after kept away from the stress environment. The ulceration indexes in the 5 and 7-hour progesterone groups were （19.1±10.5） and （11.9±9.7） respectively, which were obviously decreased as compared with that in the 0-hour stress group. The ulceration index in the 7-hour progesterone group was obviously decreased as compared with that in the 7-hour saline group. （3） The contracted frequency and modulation of the isolated mice duodenal smooth in the normal control group were （50.0±9.5） beats per minute and （3.24±1.3） mm, respectively. As compared with the control group, the contracted frequency and modulation of the isolated mice duodenal smooth were obviously reduced in a concentration-dependent manner in the progesterone groups （5, 50, 100 μmol /L） [（37.7±11.7） beats per minute, （2.78±1.1） mm; （34.08±2.6） beats per minute, （2.65±0.4） mm; （25.13±2.4） beats per minute, （2.67±0.9） mm], suggesting that progesterone could inhibit the contractility of isolated duodenal smooth muscle. CONCLUSION： Progesterone plays the protective and therapeutic roles in stress gastric ulcers, and its possible mechanism may be related to its effect in inhibiting the contractility of gastroduodenal smooth muscle, but have nothing to do with the secretion of gastric acid.