腹泻型肠易激综合征大鼠模型不同造模方法的比较研究

Research of Different Modeling Methods of Rats with Diarrhea-predominant Irritable Bowel Syndrome

目的：对比分析腹泻型肠易激综合征（IBS-D）大鼠模型不同造模方法的差异,探索符合IBS-D临床特征的造模方法。方法：70只新生期乳鼠被随机分成正常组、番泻叶高剂量组、中剂量组、低剂量组、高乳糖饲养组、醋酸溶液灌肠组、腹腔注射5羟色胺（5-HT）组。除正常组外,其余各组出生后第2-14天均接受母子分离应激3 h,2个月后番泻叶高剂量组给予番泻叶煎剂4.5 g/kg、中剂量组给予3 g/kg、低剂量组给予2 g/kg灌胃,灌胃体积为10 mL/kg,连续7 d,给予普通饲料喂养;高乳糖组采用高乳糖饲料喂养,7 d后换用普通饲料;醋酸灌肠组给予4%的醋酸灌肠1 mL,灌肠1次,普通饲料喂养,此后不做任何处理;5-HT腹腔注射组给予5-HT 2.1mg/kg腹腔注射,连续7 d,普通饲料喂养,从大鼠体质量增长情况、腹泻率及大便积分、结肠病理几个方面对模型进行评价。结果：（1）与正常组大鼠相比,除番泻叶低剂量组大鼠体质量无明显变化外,其余各组体质量增长量均显著降低,具有显著性差异（P〈0.01）,其中高乳糖饲料组和醋酸灌肠组大鼠体质量出现明显的负增长;（2）番泻叶高剂量组（4.5 g/kg）、高乳糖饲料组和醋酸灌肠组大鼠腹泻率均为100%,其余各组均未出现腹泻。造模后番泻叶高剂量组和醋酸灌肠组大鼠6 d内的平均大便积分显著高于正常组,具有显著性差异（P〈0.05）;（3）结肠病理高乳糖组可见淋巴细胞、中性粒细胞和嗜酸性粒细胞浸润,细胞间质轻度水肿;醋酸灌肠组部分结肠与腹腔组织粘连、增厚,结肠缩短,近端结肠可见黏膜轻度充血,绒毛变钝,其余各组未见异常。结论：新生期母子分离应激联合适当剂量番泻叶灌胃或高乳糖饲料饲养所致大鼠模型可模拟IBS-D的主要临床特征,是建立IBS-D较为理想的造模方法。

Objective：To explore a reliable method of establishing a rat model which characteristics were accorded with IBS-D patients. Methods：Seventy neonatal rats were randomly divided into 7 groups： normal group,senna high dose group,senna middle dose group,senna low dose group,lactose group,acetic acid group,5-HT group. There were 10 rats in each group. Pups were exposed to a 3 h period of daily maternal separation on postnatal day 2-14 except the normal group. The next treatments were performed at 2 months of age. The senna high dose group was given 4. 5 g/kg Senna Decoction by gavage for 7 days. The senna middle dose group was given 3 g/kg Senna Decoction and the senna low dose group was given 2 g/kg Senna Decoction. The lactose group was given lactose enriched diet for 7 days. The acetic acid group was given 4% acetic acid 1 mL by anus once. The 5-HT group was given 2. 1 mg/kg 5-HT by intraperitoneal injection for 7 days. The diarrhea rate was evaluated during the process. The stool consistency was observed and the fecal score was calculated after the modeling for 1 week. The growth of body mass and pathologic features of the proximal were evaluated after the modeling. Results：（1） Except the senna low dose group,the weight growth of all the other groups decreased significantly compared to that of the normal group（P〈0. 01）. Negative growth was observed in the lactose group and acetic acid group.（2） The diarrhea rate of the senna high dose group,lactose group and acetic acid group was100%. There was no diarrhea in the other groups. The average fecal score of the senna high dose group and acetic acid group was significantly higher compared to that of the normal group after the modeling（P〈0. 05）.（3） The infiltration of lymphocytes,neutrophils,eosnophils and interstitial edema were observed in colon of the lactose group,tissue adhesions and proliferation were observed in the acetic acid group. The other groups had no abnormal changes. Conclutions：Neonatal maternal separation and senna by gavage or lactose enriched diet were reliable to duplicate a rat model of IBS-D.