Jianpiliqi formula suppresses low-grade inflammation and restores epithelial barrier integrity in the duodenum of rats with functional dyspepsia
Background Chinese medicine Jianpiliqi(JPLQ)formula has shown strong therapeutic effects in the treatment of functional dyspepsia(FD).However,little is known about the underlying mechanisms.Recent reports have demonstrated that impaired duodenal mucosal integrity and low-grade inflammation contribute to the pathogeneses of FD.We investigated whether JPLQ formula could restore duodenal mucosal integrity and suppress low-grade inflammation associated with FD and further assessed the potential molecular mechanisms in rats.Methods Rats with FD were generated via stress-based tail clamping.Stressed rats were given JPLQ or saline in the drinking water for 7 days,and then transepithelial electric resistance(TEER)was measured by Ussing chamber.Protein expression was determined by Western blotting and immunofluorescence,and mRNA expression was analyzed by quantitative reverse transcription PCR(qRT-PCR).Inflammatory cytokine expression was measured by Enzyme-linked immunesorbent assay(ELISA).Results TEER was increased in JPLQ-treated stressed rats as compared to the control-treated stressed rats.The expression of tight junction proteins,claudin-1 and occludin,in the duodenum of stressed rats was significantly higher than that in control rats.Moreover,JPLQ treatment attenuated the production of tumor necrosis factor alpha(TNF-α)and interferon gamma(INF-y)in duodenal mucosa.Mast cells acts as a key effector in stress-induced mucosal injury and inflammation.The number of mast cells in the duodenum as revealed by staining of tryptase was significantly increased in stressed rats relative to the control rats,but JPLQ treatment mitigated the increase in mast cell infiltration.A concurrent decrease in response to JPLQ was also found in the mRNA expression of tryptase and protease-activated receptor 2(PAR2),which mediate proinflammatory responses.Conclusions The therapeutic effects of JPLQ formula on FD are at least partially through the improvement of duodenal mucosal integrity and the attenuation of low-grade inflammation in the duodenum by suppressing mast cell infiltration and the activation of the tryptase-PAR2 axis.Our findings have thus highlighted the molecular basis of JPLQ-based treatment of FD in human patients.
Jianpiliqi formula functional dyspepsia tight junction mast cell inflammation
Lu-Qing Zhao Xiong-Fei Chang Sheng-Sheng Zhang Chun-Yang Zhu
国内会议
中华中医药学会内科分会2018年学术年会暨董建华学术传承研讨会
北京
英文
73-81
2018-11-01（万方平台首次上网日期，不代表论文的发表时间）