To investigate the modeling methods and clinical significance of animal models of anal incontinence.

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.

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.

Both sphincter severing and sacral nerve injury are effective in establishing porcine models of anal incontinence. Regulation of lipolysis in adipocytes, PPAR signaling pathway, TGF-beta signaling, Spliceosome, and other signaling pathways may be involved in the occurrence of anal incontinence, but the specific mechanisms need to be further studied.