Ursodeoxycholic acid protects interstitial Cajal-like cells in the gallbladder from undergoing apoptosis by inhibiting TNF-α expression
Ursodeoxycholic acid protects interstitial Cajal-like cells in the gallbladder from undergoing apoptosis by inhibiting TNF-α expression
复制标题
熊去氧胆酸通过抑制 TNF-α 表达来保护胆囊中的间质 Cajal 样细胞免于凋亡
DOI：
10.1038/aps.2017.206
复制
发表时间：
2018-09-01
影响因子：
8.2
通讯作者：
Chen, Nai-hong
中科院分区：
文献类型：
--
作者：
Wan, Jiang-fan;Chu, Shi-feng;Chen, Nai-hong
动力减退是胆石病的常见症状，伴随着胆囊内间质Cajal样细胞(ICLC)的丢失。熊去氧胆酸(UDCA)被广泛用于治疗胆石症，除了溶解胆结石外，还具有抗细胞凋亡和抗炎的作用。在本研究中，我们研究了UDCA对胆结石豚鼠ICLCs的抗凋亡和抗炎作用。以高胆固醇饲料喂养豚鼠8周，诱发胆结石形成。一组动物同时给予UDCA(50 mg·kg-1−·d-−-1，ig)。8周末麻醉下安乐死动物，立即行胆囊切除术，取胆汁作进一步分析。结果表明，模型组大鼠胆囊肌对乙酰胆碱(ACh)和CCK-8的收缩反应严重受损，UDCA可显著改善其收缩反应。此外，根据凋亡细胞和c-kit阳性细胞的共定位成像观察，UDCA显著降低了ICLCs的凋亡率。Western blotting分析和实时定量聚合酶链式反应结果显示，UDCA处理的动物肿瘤坏死因子-α/Caspase8/Caspase3途径受到抑制，证实了UDCA在胆囊壁中的抗细胞凋亡作用。H&E染色显示，UDCA组大鼠胆囊壁炎症细胞浸润明显减轻。结论：UDCA可通过抑制肿瘤坏死因子-α/Caspase8/Caspase3途径，保护胆囊壁ICLC免受细胞凋亡的影响。
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.