消化道多维振动胶囊设计与便秘模型犬实验观察

Design of digestive tract multi-dimensional vibration capsule and experimental observation of constipation canine model

目的探讨自主设计的多维振动胶囊对慢性便秘模型犬的安全性和有效性。方法采用自主设计的口服多维振动胶囊,结构由2个功能子系统组成:体外的控制和无线供能子系统,体内的无线能量接收储存和按需振动子系统;胶囊尺寸L19 mm×Φ11.2 mm;质量<4 g;振动频率3次/分;振动强度0.294~0.490 N,最大瞬间力≤2.157 N;静默时间0~12 h可调;工作时间,自带电池连续工作72 h,在体可工作84 h(静默时间+连续工作时间)。选择12只雌性比格犬,体质量(16.2±2.6)kg。按数字随机法分为健康对照组(A组)、健康犬安全性评价组(B组)、便秘对照组(C组)、便秘治疗组(D组),每组各3只。对B组和D组犬给以每周2粒胶囊喂饲,连续8周,与A组和C组比较,观察多维振动胶囊喂饲后模型动物的饮水、运动状态,定时进行排出胶囊计数、大便性状评分,实验结束后获取结肠组织病理检测黏膜厚度、肌间神经丛及黏膜完整性。结果喂饲胶囊均正常工作,B组和D组犬均顺利排出所有口服的多维振动胶囊,该胶囊没有破损。D组犬口服多维振动胶囊后大便Bristol评分显著改善,4周和8周明显优于A组和治疗前(实验4周后与制模成功后比较,3.33分±1.52分vs 1.67分±1.55分;P=0.023。实验8周后与制模成功后比较,5.67分±1.15分vs 1.67分±0.58分;P=0.013);C组喂饲4周后大便Bristol评分增加(6.00分±1.00分vs 4.00分±1.00分;P=0.025),但8周后大便Bristol评分恢复(4.67分±0.58分vs 4.00分±1.00分;P=0.101);D组在前4周排出的多维振动胶囊数量明显少于B组(20颗vs 26颗;P<0.001),后4周多于C组(28颗vs 22颗,P=0.002)。病理切片显示多维振动胶囊治疗可增加慢性便秘治疗组结肠壁黏膜厚度,改善便秘黏膜的连贯性破坏和杯状细胞的减少,多维振动胶囊治疗可明显改善便秘导致的结肠肌间神经元的退化。结论多维振动胶囊口服安全,能明显改善慢性便秘模型犬的粪便传输,具有较好的临床应用潜力。

Objective To investigate safety and effectiveness of self-designed multi-dimensional vibration capsule for chronic constipation canine model.Methods Self-designed oral multi-dimensional intestinal vibration capsule was adopted,which consisted of 2 functional subsystems:in vitro control and wireless energy supply subsystem,in vivo wireless energy receiving,storage and on-demand vibration subsystem.The capsule size was L19 mm×Φ11.2 mm;mass<4 g,vibration frequency of 3 times/minute,vibration strength of 0.294-0.490 N,maximum instantaneous force≤2.157 N,silence time of 0-12 hours(adjustable);working time:continuous working for 72 hours with battery,in vivo working time of 84 hours(silent time+continuous working time).Twelve female beagles with body weight of(16.2±2.6)kg were randomly divided into healthy control group(group A),healthy canine safety evaluation group(group B),constipation control group(group C)and constipation treatment group(group D)by numerical method,with 3 in each group.Group B and group D were fed 2 capsules per week for 8 weeks.Compared with group A and group C,the drinking,exercise status,regular counting of discharged capsules,fecal traits score of multi-dimensional vibration capsule models were observed and evaluated.After experiment,the colon histopathological test was carried out to detect the mucosal thickness,myenteric plexus and mucosal integrity.After the experiment,the colonic tissue mucosal thickness,myenteric plexus and mucosal integrity were obtained for pathological examination.Results All capsules worked normally,and the capsules were defecated successfully in group B and group D without any damage.The stool Bristol score of group D was significantly improved after treated oral capsules,which at 4-week and 8-week were significantly better than those of group A and before treatment(4-week feeding and successful modeling:3.33 scores±1.52 scores vs 1.67 scores±1.55 scores;P=0.023.8-week feeding and successful modeling:5.67 scores±1.15 scores vs 1.67 scores±0.58 scores;P=0.013).In group C,stool Bristol score was increased after feeding for 4 weeks(6.00 scores±1.00 scores vs 4.00 scores±1.00 scores;P=0.025),but return to original value after feeding for 8 weeks(4.67 scores±0.58 scores vs 4.00 scores±1.00 scores;P=0.101).The number of capsules defecated in group D at the first 4 week was significantly less than that in group B(20 vs 26;P<0.001),and more than that in group C at the last 4 week(28 vs 22,P=0.002).The pathological test results of group D showed that capsule treatment increased colonic mucosa thickness,improved continuous destruction of constipation mucosa and decreased goblet cells,and degeneration of colonic myenteric neurons caused by constipation was significantly improved.Conclusion It is demonstrated that multi-dimensional vibration capsule is safe for oral administration,and can significantly improve fecal moving in model canine with chronic constipation,which has good clinical application potential.