Sini-san improves duodenal tight junction integrity in a rat model of functional dyspepsia.
Sini-san improves duodenal tight junction integrity in a rat model of functional dyspepsia.
复制标题
四逆散改善功能性消化不良大鼠模型的十二指肠紧密连接完整性
DOI：
10.1186/s12906-017-1938-2
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发表时间：
2017-08-30
影响因子：
--
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Chang X;Zhao L;Wang J;Lu X;Zhang S
研究背景近年来的研究表明，十二指肠粘膜屏障功能受损和局部微炎症是功能性消化不良（FD）的发病机制之一。因此，恢复正常屏障完整性成为FD治疗中的潜在治疗策略。四逆散（SNS）是一种治疗FD的中药方剂，但其作用机制尚不清楚。方法采用夹尾法建立FD大鼠模型，通过测定内脏敏感性和胃顺应性评价SNS的治疗作用。通过Ussing室测量显示上皮屏障完整性的跨上皮电阻（TEER）。通过免疫印迹和免疫荧光法测定十二指肠紧密连接（TJ）蛋白，闭合蛋白和claudin-1的表达。采用酶联免疫吸附法（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。采用定量真实的时间-聚合酶链反应（qPCR）检测FD大鼠胃黏膜瞬时受体电位香草酸1型（TRPV 1）mRNA水平。FD大鼠TEER降低，SNS治疗后TEER恢复正常，claudin和claudin-1表达恢复正常。此外，SNS还能改善FD相关的TNF-α、IFN-γ的产生和TRPV 1的表达。结论SNS治疗FD的作用至少部分是通过改善TJ的完整性和减轻FD相关的十二指肠低度炎症。我们的研究结果强调了基于SNS的FD治疗人类患者的分子基础。
BackgroundRecent 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.MethodsFD 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).ResultsSNS 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.ConclusionsThe 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.
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影响因子：
29.4
作者：
Schmitz, H;Barmeyer, C;Schulzke, JD
通讯作者：
Schulzke, JD
中药方四逆散中芍药苷对小鼠接触性皮炎作用的剖析。
影响因子：
6.1
作者：
Sun, Yang;Dong, Yi;Xu, Qiang
通讯作者：
Xu, Qiang
影响因子：
--
作者：
Lin HJ;Kao ST;Siao YM;Yeh CC
通讯作者：
Yeh CC
影响因子：
4.3
作者：
Mahadeva, Sanjiv;Goh, Khean-Lee
通讯作者：
Goh, Khean-Lee
影响因子：
24.5
作者：
Vanheel, Hanne;Vicario, Maria;Farre, Ricard
通讯作者：
Farre, Ricard