AUTHOR=Tu Jiamin , Jiang Yinping , Tu Lei , Chen Yafeng , Pan Liyun , Fan Xinjuan , Tian Jiyun , Li Jianguo , Wang Xinji , Fu Honghao , Xu Bing , Feng Dianxu 

TITLE=Da-Cheng-Qi decoction improves severe acute pancreatitis capillary leakage syndrome by regulating tight junction-associated proteins

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1138251

DOI=10.3389/fphar.2024.1138251

ISSN=1663-9812

ABSTRACT=<sec><title>Background and aims:</title><p>To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome.</p></sec><sec><title>Methods:</title><p>In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2 h pre-modeling and 2 and 4 h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD.</p></sec><sec><title>Results:</title><p>Serum levels of amylase, TNF–α, IL-1β, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (<italic>p</italic> &lt; 0.05). DCQD treatment significantly attenuated rat pancreas damage (<italic>p</italic> &lt; 0.05) and reduced tissue capillary permeability compared to the SAP group (<italic>p</italic> &lt; 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (<italic>p</italic> &lt; 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (<italic>p</italic> &lt; 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression <italic>in vitro</italic> (<italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusion:</title><p>DCQD can improve capillary permeability in both <italic>in vivo</italic> and <italic>in vitro</italic> models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.</p></sec>