Da-Huang-Fu-Zi-Tang Ameliorates Severe Acute Pancreatitis by Elevation of M2 Kupffer Cells in Rats

INTRODUCTION: Severe acute pancreatitis (SAP) is a clinical emergency often accompanied by inflammatory response syndrome (SIRS), which eventually leads to acute lung injury and failure of other organs. The activation of liver Kupffer cells (KCs) plays a major role in the process of SIRS and multiorgan damage caused by SAP. Da-Huang-Fu-Zi-Tang (DHFZT), a traditional Chinese prescription, has been widely used for SAP in the clinic. The present study investigated the activation state of KCs in SAP and the potential mechanism of DHFZT. METHODS: A total of 24 Sprague Dawley rats were randomly assigned to four groups: SH (sham operation group + saline enema), SH-DHFZT (sham operation group + DHFZT enema), SAP (model group + saline enema), and SAP-DHFZT (model group + DHFZT enema). Blood samples were drawn from the abdominal aorta for measuring serum endotoxin, amylase, calcium ion, IL-1β, TNF-α, iNOS, and IL-10. Then, the pancreas, lung, liver, and ileum were harvested for histological observation, and the liver was used to detect the level of F4/80, CD86, and CD163 in KCs with immunohistochemistry and western blot. RESULTS: In the SAP group, the CD86+ KCs were significantly increased with a high level of IL-1β, TNF-α, and iNOS, and the organs were impaired. In the SAP-DHFZT group, CD163+ KCs were significantly increased with the high level of IL-10, and the damage to organs was alleviated. CONCLUSION: These phenomena suggested that the SIRS and multiple organ damage in SAP might be related to the excessive activation of M1 KCs, and DHFZT might alleviate the SIRS by inducing the differentiation of KCs into the M2-type and promote the expression of anti-inflammatory factor IL-10.