Hypomotility is a common symptom of gallstone disease, which is accompanied by a loss of interstitial Cajal-like cells (ICLCs) in the gallbladder. Ursodeoxycholic acid (UDCA) is widely used in treating gallstone disease, and has shown anti-apoptotic and anti-inflammatory effects apart from its ability to dissolve gallstones. In this study, we investigated the anti-apoptotic and anti-inflammatory effects of UDCA on ICLCs in guinea pigs with gallstones. Guinea pigs were fed a high-cholesterol diet for 8 weeks to induce the formation of gallstones. A group of animals was administered UDCA (50 mg·kg^-1·d^-1, ig) simultaneously. At the end of 8 weeks, the animals were euthanized with anesthesia, cholecystectomy was performed immediately and gallbladder was collected for further analysis. We showed that in the model group the contractility of gallbladder muscle strips in response to both acetylcholine (ACh) and CCK-8 was severely impaired, which was significantly improved by UDCA administration. Furthermore, UDCA administration significantly reduced the apoptotic ratio of ICLCs, based on the observation of co-localization imaging of apoptotic cells and c-kit-positive cells. Western blotting analysis and real-time PCR results revealed that the TNF-α/Caspase8/Caspase3 pathway was suppressed in the UDCA-treated animals, confirming the anti-apoptotic effect of UDCA in the gallbladder. The H&E staining showed that UDCA administration significantly attenuated inflammatory cell infiltration in the gallbladder wall. In conclusion, UDCA can protect ICLCs in the gallbladder from undergoing apoptosis by inhibiting the TNF-α/Caspase8/caspase3 pathway.

中文翻译：

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熊去氧胆酸通过抑制TNF-α的表达来保护胆囊间质Cajal样细胞免于凋亡。

低动力性是胆结石疾病的常见症状，并伴有胆囊间质Cajal样细胞（ICLC）的丢失。熊去氧胆酸（UDCA）被广泛用于治疗胆结石疾病，除具有溶解胆结石的能力外，还显示出抗凋亡和抗炎作用。在这项研究中，我们调查了UDCA对豚鼠胆结石的ICLCs的抗凋亡和抗炎作用。给豚鼠饲喂高胆固醇饮食8周，以诱导其形成胆结石。一组动物给予UDCA（50 mg·kg ^-1 ·d ^-1，ig）同时进行。在8周结束时，对动物实施安乐死，立即进行胆囊切除术，并收集胆囊用于进一步分析。我们显示，在模型组中，胆囊肌条对乙酰胆碱（ACh）和CCK-8的反应均受到严重损害，而UDCA给药可显着改善胆囊肌条的收缩能力。此外，根据对凋亡细胞和c-kit阳性细胞共定位成像的观察，施用UDCA可以显着降低ICLC的凋亡率。Western印迹分析和实时PCR结果表明，在UDCA处理的动物中TNF-α/ Caspase8 / Caspase3途径被抑制，证实了UDCA在胆囊中的抗凋亡作用。H＆E染色显示UDCA给药显着减弱了胆囊壁中的炎性细胞浸润。总之，UDCA可以通过抑制TNF-α/ Caspase8 / caspase3途径来保护胆囊中的ICLC免受凋亡。