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      Modified Da-chai-hu Decoction regulates the expression of occludin and NF-κB to alleviate organ injury in severe acute pancreatitis rats

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          Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·L –1 vs (5626.4 ± 795.1) U·L –1], DAO [(1100.1 ± 334.3) U·L –1 vs (1666.4 ± 525.3) U·L –1] and CRP [(7.6 ± 1.2) µg·mL –1 vs (17.8 ± 3.8) µg·mL –1]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mL –1 vs (90.1 ± 14.9) pg·mL –1] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 May 2019
          : 17
          : 5
          : 355-362
          1 Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
          2 Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China
          3 Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
          4 Department of Clinical Laboratory, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
          Author notes
          *Corresponding author: ZHANG Shu-Kun, E-mail: shu1971@

          ΔThese authors contributed equally to this work.

          These authors have no conflict of interest to declare.

          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 81703846
          This work was supported by the Key Research Lab of State Administration of Traditional Chinese, Comprehensive Investment Subject Construction Project of Tianjin Medical University (2016-2020) and the National Natural Science Foundation of China (No. 81703846).


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