Dai-Huang-Fu-Zi-Tang alleviates pulmonary and intestinal injury with severe acute pancreatitis via regulating aquaporins in rats

Abstract

BackgroundDai-Huang-Fu-Zi-Tang (DHFZT) is a famous traditional Chinese prescription with intestinal obstruction, acute pancreatitis and cholecystalgia for thousands of years. Our previous work found that DHFZT could act against pulmonary and intestinal pathological injury in rats with severe acute pancreatitis (SAP). But the underlying mechanism has not been fully elucidated. The aim of present study was to investigate whether DHFZT could relieve pulmonary and intestinal injury by regulating aquaporins after SAP induced by sodium taurocholate in rats.MethodsForty of SD rats were used for dose dependant experiments of DHFZT.Accurate-mass Time-of-flight liquid chromatography-mass spectrometry was used for qualitative screening of chemical compositions of DHFZT. Twenty-four rats were randomly divided into 3 groups: sham group (n = 8), model group (SAP, n = 8), DHFZT group (SAP with DHFZT treatment, n = 8). SAP models were established by retrograde injections of 5% sodium taurocholate solutions into rat pancreaticobiliary ducts. Blood samples were taken at 0, 12, 24, 48 h post-operation for detecting serum amylase, lipase, endotoxin, TNF-α, IL-6 and IL-10. Protein expression and location of aquaporin (AQP)1, 5, 8 and 9 were assessed by immunohistochemistry, western blot and immunofluorescence respectively.ResultsThe study showed that 27 kinds of chemical composition were identified, including 10 kinds in positive ion mode and 17 kinds in negative ion mode. The results showed that AQP1, AQP5 of lung, and AQP1, AQP5, AQP8 of intestine in model group were significantly lower than that of sham group (P < 0.05), and which were obviously reversed by treatment with DHFZT. In addition, protein levels of pro-inflammatory cytokines such as TNF-α, IL-6 and endotoxin in peripheral blood were significantly suppressed by DHFZT, and that anti-inflammatory cytokine like IL-10 was just opposite. Finally, we also noted that DHFZT reduced serum levels of amylase, lipase and endotoxin, and also improved edema and pathological scores of lung and intestine after SAP.ConclusionsDHFZT ameliorated the pulmonary and intestinal edema and injury induced by SAP via the upregulation of different AQPs in lung and intestine, and suppressed TNF-α, IL-6 expression and enhanced IL-10 expression.

Function of aquaporins in sepsis: a systematic review

“…unknown regulation, = unaffected) Aquaporin Tissue Regulation during inflammation References AQP1 Immune cells ↑ In leukocytes and cell lines (THP-1) [ 8 , 9 ] Heart ↑ In cardiac cells [ 58 ] Lung ↓ In lung tissue after LPS [ 5 , 6 ] AQP2 Kidney ↓ In renal tissue after LPS [ 37 ] AQP3 Immune cells ↓ In leukocytes of septic patients [ 8 ] AQP4 Brain ↑ In brain and anterior pituitary gland [ 31 , 75 ] AQP5 Lung ↓ In lung tissue after LPS [ 65 ] Immune cells ↓ In THP-1 cells after LPS [ 9 ] AQP7 Immune cells ? Mouse resident peritoneal macrophages [ 76 ] AQP8 Liver ↓ In hepatic cells [ 11 ] Lung = In bronchial epithelial cells [ 61 ] AQP9 ...…”

“…In lung mainly the aquaporins AQP1 and 5, 8 and to a lower extent AQP9 are expressed [ 60 ]. Here, Aqp1 is expressed in all vascular endothelial cells, Aqp5 in the alveolar type I cells and Aqp8 and Aqp9 can be found in the bronchial epithelial cells in lung [ 61 ] (Fig. 2 c).…”

“…As a therapeutic option it was demonstrated that hydrogen rich saline and parenteral vitamin C can be protective in sepsis related lung injury and that it can attenuate the LPS induced reduction of Aqp1 and Aqp5 expression [ 5 , 68 ]. In addition, Aqp1 and Aqp5 expression in lung is reduced in lung after an inflammatory pancreatitis models, whereas Aqp8 and Aqp9 expression remains unaffected [ 61 ]. Here the traditional Chinese prescription Dai-Huang-Fu-Zi-Tang can upregulate Aqp1 and 5 and attenuate inflammation [ 61 ].…”

“…In addition, Aqp1 and Aqp5 expression in lung is reduced in lung after an inflammatory pancreatitis models, whereas Aqp8 and Aqp9 expression remains unaffected [ 61 ]. Here the traditional Chinese prescription Dai-Huang-Fu-Zi-Tang can upregulate Aqp1 and 5 and attenuate inflammation [ 61 ].…”

Dai‐Huang‐Fu‐Zi‐Tang Alleviates Intestinal Injury Associated with Severe Acute Pancreatitis by Regulating Mitochondrial Permeability Transition Pore of Intestinal Mucosa Epithelial Cells

“…DHFZT was composed of three herbs including Radix et Rhizoma Rhei (DH), Radix Aconiti Lateralis Preparata (FZ), and Radix et Rhizoma sari (XX), and it was originally described in the Synopsis of Golden Chamber (Jin Kui Yao Lue), which was a treatise on febrile and miscellaneous diseases written by the outstanding physician Zhang Zhongjing in Han Dynasty. Our previous study revealed that DHFZT markedly alleviates intestinal injury with severe acute pancreatitis via regulating aquaporins in rats [ 15 ]. However, the effect of DHFZT on intestinal injury with severe acute pancreatitis via regulating MPTP has not yet been entirely clear.…”