Chang Xiongfei, Zhao Luqing, Wang Jiajia, Lu Xiaofang, Zhang Shengsheng
Beijing University of Chinese Medicine, Beijing, China.
Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China.
BMC Complement Altern Med. 2017 Aug 30;17(1):432. doi: 10.1186/s12906-017-1938-2.
Recent reports have demonstrated that impaired barrier function and local microinflammation in the duodenal mucosa contribute to the pathogeneses of functional dyspepsia (FD). Thus, restoring normal barrier integrity becomes a potential therapeutic strategy in the treatment of FD. Sini-San (SNS) is a traditional Chinese prescription that exhibits therapeutic effects in FD, but the underlying mechanisms remain not well understood.
FD rats were established by tail clamping method and the therapeutic effect of SNS was evaluated by measuring the visceral sensitivity and gastric compliance. Transepithelial electrical resistance (TEER) that reveals epithelial barrier integrity was measured by Ussing chamber. The expression of tight junction (TJ) proteins, occludin and claudin-1, in the duodenum was determined by Western blot and immunofluorescence. The amount of tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in duodenal mucosa was detected by enzyme-linked immune sorbent assay (ELISA). The mRNA level of transient receptor potential vanilloid type 1 (TRPV1) was measured by quantitative real time-polymerase chain reaction (qPCR).
SNS could improve gastric compliance and attenuate visceral hypersensitivity (VH) in FD rats. TEER was decreased in FD rats, but treatment with SNS restored normal level of TEER and the expression of occludin and claudin-1 in FD rats. In addition, SNS administration ameliorated FD-associated increase in the production of TNF-α, IFN-γ and the expression of TRPV1.
The therapeutic effect of SNS on FD is at least partially through improvement of TJ integrity and attenuation of FD-associated low-grade inflammation in the duodenum. Our findings highlight the molecular basis of SNS-based treatment of FD in human patients.
近期报告表明，十二指肠黏膜屏障功能受损和局部微炎症参与功能性消化不良（FD）的发病机制。因此，恢复正常的屏障完整性成为治疗FD的一种潜在治疗策略。四逆散（SNS）是一种传统中药方剂，对FD具有治疗作用，但其潜在机制尚不完全清楚。
采用夹尾法建立FD大鼠模型，通过测量内脏敏感性和胃顺应性评估SNS的治疗效果。使用尤斯灌流小室测量反映上皮屏障完整性的跨上皮电阻（TEER）。通过蛋白质免疫印迹法和免疫荧光法测定十二指肠中紧密连接（TJ）蛋白occludin和claudin-1的表达。采用酶联免疫吸附测定法（ELISA）检测十二指肠黏膜中肿瘤坏死因子α（TNF-α）和干扰素γ（INF-γ）的含量。通过定量实时聚合酶链反应（qPCR）测量瞬时受体电位香草酸亚型1（TRPV1）的mRNA水平。
SNS可改善FD大鼠的胃顺应性并减轻内脏超敏反应（VH）。FD大鼠的TEER降低，但SNS治疗可恢复FD大鼠的TEER正常水平以及occludin和claudin-1的表达。此外，给予SNS可改善FD相关的TNF-α、IFN-γ产生增加以及TRPV1的表达。
SNS对FD的治疗作用至少部分是通过改善TJ完整性和减轻十二指肠中与FD相关的低度炎症实现的。我们的研究结果突出了SNS治疗人类FD患者的分子基础。
