肛门失禁大动物模型的建立  

Establishment of a large animal model of anal incontinence

作　　者：路明[1] 杨博[1] 刘扬[1] 王慧[1] 洪文[1] 黄克林 刘青[1] Lu Ming;Yang Bo;Liu Yang;Wang Hui;Hong Wen;Huang Kelin;Liu Qing(Department of Proctology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院肛肠科,乌鲁木齐830054

出　　处：《中华临床医师杂志（电子版）》2022年第4期356-361,共6页Chinese Journal of Clinicians(Electronic Edition)

基　　金：新疆维吾尔自治区自然科学基金(2020D14007)。

摘　　要：目的探讨肛门失禁动物模型的造模方式及其临床意义。方法本文采用两种方法进行肛门失禁巴马小型猪模型的创建,分别为通过外科手术操作对小型猪的肛门括约肌离断致猪肛门失禁动物模型的创建和骶神经麻醉药物注射的方法对小型猪的骶神经损伤所致猪肛门失禁动物模型的创建,对猪肛门失禁动物模型进行肛门静息压测定,并取肛门括约肌组织进行组织形态学检测及可变剪接基因检测。结果括约肌离断法与骶神经损伤法均诱导巴马小型猪发生肛门失禁,具体表现为大便不能自行控制(括约肌离断组:第1天出现肛门失禁,第2~14天保持肛门失禁。骶神经损伤组:第1天出现不完全大便失禁,第2~6天开始大便失禁情况逐渐加重,至第7天出现完全肛门失禁,第8~14天均保持肛门失禁状态)、肛门静息压显著降低(骶神经损伤组10.29±0.23 mmHg,括约肌离断组7.32±0.53 mmHg均<对照组26.31±2.58 mmHg)和括约肌组织形态破坏(肛门括约肌组织形态结构异常,括约肌全层变薄,固有层结缔组织变厚,肌纤维数量明显减少、变细、断裂,横纹肌致密程度明显下降)。括约肌离断法较骶神经损伤法诱导肛门失禁速度更快,并且肛门静息压更低。模型组与对照组肛门组织可变剪接基因检测结果显示存在可变剪接差异基因,京都基因和基因组百科全书(KEGG)富集分析表明,差异可变剪接基因富集于Regulation of lipolysis in adipocytes、PPAR signaling pathway、TGF-beta signaling pathway、Spliceosome等信号通路。结论括约肌离断法和骶神经损伤均可有效的进行猪肛门失禁动物模型的建立,Regulation of lipolysis in adipocytes、PPAR signaling pathway、TGF-beta signaling pathway、Spliceosome等信号通路异常的可变剪接可能参与肛门失禁的发生,具体机制有待深入研究。Objective To investigate the modeling methods and clinical significance of animal models of anal incontinence.Methods This study adopted two methods for the creation of an Obama miniature pig model of anal incontinence:surgical severing of the anal sphincter(sphincter severing group)and sacral anesthesia drug injection(sacral nerve injury group).The anal resting pressure was measured,the anal sphincter tissue was detected by histomorphology,and differentially expressed alternatively spliced genes were detected.Results Both surgical severing of the anal sphincter and sacral anesthesia drug injection induced anal incontinence in Bama miniature pigs,which was manifested as uncontrollable defecation(sphincter severing group:anal incontinence started to occur on day 1 and was maintained on days 2-14;sacral nerve injury drug injection group:incomplete fecal incontinence appeared on day 1 and gradually worsened from day 2 to day 6,and complete anal incontinence appeared on day 7 and remained on days 8-14).Anal resting pressure decreased significantly in both groups compared with control animals[sacral nerve injury group:(10.29±0.23)mmHg;sphincter severing group:(7.32±0.53)mmHg;control animals:(26.31±2.58)mmHg].The morphology of the anal sphincter was damaged:the morphological structure of the anal sphincter was abnormal,the whole layer of the sphincter was thinner,the connective tissue of the lamina propria was thicker,the muscle fibers was significantly reduced in number,thin,and broken,and the density of the striated muscle was significantly decreased.Sphincter severing induced anal incontinence more quickly and with lower anal resting pressure than sacral nerve injury.There were differential alternatively spliced genes,and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes showed that the differential alternatively spliced genes were enriched in Regulation of lipolysis in adipocytes,PPAR signaling pathway,TGF-beta signaling pathway,Spliceosome,and other signaling pathways.Conclusion Both sphincter seve

关 键 词：肛门失禁 动物模型 组织形态学 

分 类 号：R657.1[医药卫生—外科学]