雌酚酮衍生物EA303对小鼠腹泻的抑制作用  

Anti-diarrhea effect of EA303 (an estrone derivative) in mice

作　　者：朱岚[1] 付守廷[1] 李建婷[1] 韦元元[1] 王冰[1] 汪慧慧[1] 陈国良[1] 

机构地区：[1]沈阳药科大学生命科学与生物制药学院,辽宁省沈阳市110016

出　　处：《世界华人消化杂志》2009年第26期2727-2731,共5页World Chinese Journal of Digestology

摘　　要：目的:研究雌酚酮衍生物EA303对小鼠腹泻的抑制作用及机制.方法:采用小鼠的蓖麻油、硫酸钠、液体石蜡等腹泻模型及炭末推进法观察低、中、高剂量(14.87mg/kg、29.74mg/kg、59.48mg/kg)的EA303对小鼠在体内胃肠道的作用.通过离体运动实验法分析不同浓度(10-5mol/L、3×10-5mol/L、10-4mol/L)的EA303对家兔离体肠道平滑肌的作用.结果:EA303高、中、低3个剂量组灌胃给药后在不同时间段与生理盐水组相比可明显降低蓖麻油、硫酸钠、液体石蜡所致的小鼠腹泻的腹泻指数;高剂量组与生理盐水组相比可明显降低正常小鼠的小肠推进率(58.53%±14.12%vs78.41%±15.91%,P<0.01);高、中、低剂量组与生理盐水组相比均可明显延缓正常小鼠的排便时间(116.40±17.69min,114.40±45.76min,101.50±50.02minvs78.10±15.98min,均P<0.01);中、高剂量的EA303与未给药前相比能显著降低小肠平滑肌自主活动的振幅(43.26%±14.83%,16.70%±10.89%vs100.00%±0.00%,均P<0.01),高剂量组与未给药前相比还显著降低小肠平滑肌自主活动的张力(58.94%±7.16%vs100.00%±0.00%,P<0.01).结论:EA303具有抑制肠运动和抗腹泻作用,其作用机制可能是降低肠管平滑肌振幅和张力.AIM： To investigate the anti-diarrhea effect of EA303 （an estrone derivative） in mice and explore the mechanisms involved. METHODS： Diarrhea was induced in mice by cathartics （castor oil, magnesium sulfate or liquid paraffin）. At various time points following oral administration of a single dose of EA303 （14.87, 29.74 or 59.48 mg/kg） , the diarrhea index was determined. The effect of EA303 on intestinal propulsion was evaluated using the charcoal meal method. The effect of different concentrations of EA303 （10-5, 3 × 10^-5 and 10^-4 mol/L） on isolated intestinal smooth muscle of rabbits was also evaluated. RESULTS： Compared with normal saline, EA303 at various doses tested could significantly decrease diarrhea indices at various time points following dosing; high-dose EA303 （59.48 mg/kg） could significantly reduce the intestinal propulsion rate of charcoal meal in mice （58.53% ± 14.12% vs 78.41% ± 15.91%, P 〈 0.01）; and EA303 at various doses tested （high-, medium- and low-dose） could significantly postpone the defecation of mice （116.40 ± 17.69 min, 114.40 ± 45.76 min and 101.50 ± 50.02 min vs 78.10 ± 15.98 min, respectively; all P 〈 0.01）. Compared with pretreatment baseline values, EA303 at concentrations of 3 × 10^-5 mol/L and 10^-4 mol/L significantly inhibited the contraction amplitude of isolated intestinal smooth muscle from rabbits （43.26% ± 14.83% and 16.70% ± 10.89% vs 100.00% ± 0.00%, respectively; both P 〈 0.01）, while EA303 at a concentration of 10^-4 mol/L significantly decreased the contraction tension of isolated intestinal smooth muscle from rabbits （58.94% ± 7.16% vs 100.00% ± 0.00%, P 〈 0.01）. CONCLUSION： EA303 can exert an anti-diarrhea effect perhaps through lowering contraction amplitude and tension of intestinal smooth muscle.

关 键 词：止泻 雌酚酮 腹泻指数 推进率 

分 类 号：R965[医药卫生—药理学]