研究动态
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Rifaximin 可预防 MCT 诱导的 HSOS 小鼠的肠屏障功能障碍并减轻肝损伤。

Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice.

发表日期:2023 Nov 11
作者: Yan-Yun Shu, Li-Lin Hu, Ling Yang, Hui-Kuan Chu, Jin Ye, Yu Jin
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

利福昔明是肝脏和肠道疾病治疗策略的有效组成部分。然而,利福昔明治疗肝窦阻塞综合征(HSOS)的疗效尚未探讨。本研究旨在探讨利福昔明治疗HSOS的疗效及机制。通过野百合碱(MCT,800 mg/kg)建立小鼠HSOS模型,并部分HSOS小鼠灌胃给予利福昔明。然后,根据肝脏病理结果、肝脏促炎细胞因子、丙氨酸转氨酶和天冬氨酸转氨酶水平评估利福昔明在 HSOS 中的疗效。使用Ussing小室评估肠道通透性,通过蛋白质印迹和实时聚合酶链反应测量紧密连接(TJ)蛋白以评估肠道屏障完整性。然后,通过酶联免疫吸附测定法评估血清促炎细胞因子水平。随后进行体外实验,确定利福昔明与TJ蛋白的关系。利福昔明有效减轻MCT诱导的HSOS肝损伤,抑制肝脏促炎细胞因子的表达,降低血清肿瘤坏死因子-α和白细胞介素的水平-6。此外,利福昔明降低肠道通透性,改善肠道屏障完整性,促进TJ蛋白表达。结果表明,MCT诱导的HSOS中肠道屏障完整性被破坏。利福昔明对 MCT 诱导的 HSOS 的显着缓解可能与通过调节 TJ 蛋白表达来修复肠道屏障完整性有关。© 2023。华中科技大学。
Rifaximin is an effective component of treatment strategies for liver and intestinal diseases. However, the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome (HSOS) has not been explored. The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS.An HSOS model was established in mice through the administration of monocrotaline (MCT, 800 mg/kg), and part of the HSOS mice were intragastrically administered with rifaximin. Then, the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings, liver proinflammatory cytokines, and alanine aminotransferase and aspartate aminotransferase levels. The Ussing chamber was used to evaluate the intestinal permeability, and tight junction (TJ) proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity. Then, the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay. Afterwards, an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins.Rifaximin effectively alleviated the MCT-induced HSOS liver injury, suppressed the expression of liver proinflammatory cytokines, and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6. Furthermore, rifaximin reduced the intestinal permeability, improved the intestinal barrier integrity, and promoted the expression of TJ proteins.The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS. The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.© 2023. Huazhong University of Science and Technology.