Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6810
Peer-review started: May 27, 2020
First decision: July 29, 2020
Revised: August 7, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: November 21, 2020
The complications acute lung injury (ALI) and acute kidney injury (AKI) caused by severe inflammation are the main reasons for high mortality of severe acute pancreatitis (SAP). These two complications can both lead to water metabolism and acid-base balance disorders, which could act as additional critical factors affecting the disease trend. Aquaporins (AQPs), which can regulate the transmembrane water transport, have been proved to participate in the pathophysiological process of SAP and the associated complications, such as ALI and AKI. Thus, exploring herbs that can effectively regulate the expression of AQPs in SAP could benefit the prognosis of this disease.
Our previous studies have demonstrated that SAP rats would be complicated with ALI, AKI, and some other manifestations of fluid metabolism disorders, such as pulmonary edema, pleural effusion, and seroperitoneum. Yue-Bi-Tang (YBT) has been widely used as a diaphoretic decoction to treat edema generated from some respiratory diseases based on the theory of traditional Chinese medicine for ages. In modern Chinese medicine treatments, YBT is directly used to treat some edema diseases resulting from kidney injury, such as acute glomerulonephritis. The question is whether YBT could alleviate ALI and AKI by regulating AQP expression in SAP rats. Therefore, this study aimed to verify the effect of YBT treatment in SAP rats complicated with ALI-AKI and explore the underlying mechanism.
To determine whether YBT can regulate the water metabolism in rats with severe acute pancreatitis via regulating expression of aquaporins.
Healthy male Sprague-Dawley rats were randomly divided into a sham-operated group (SOG), model group (MG), and YBT-treatment group (TG), with 12 rats in each group. SAP was induced with 3.5% sodium taurocholate in the MG and TG. Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline. Blood and tissue samples were harvested to detect serum inflammatory cytokines, histopathological changes, malondialdehyde and superoxide dismutase in the lung, protein and mRNA expression of kidney injury molecule-1, α-smooth muscle actin, and vimentin in the kidney, protein and mRNA expression of AQP1 and 4 in the lung, pancreas, and kidney.
The serum IL-10, TNF-α, and creatinine levels in the MG were higher than those in the SOG. Treatment with YBT could decrease TNF-α level. Malondialdehyde level in the lung was higher than that in SAP model rats. Rats of the MG had more serious pathological injury and edema in the pancreas, lung, and kidney, and higher protein expression of AQP4 in the lung and AQP1 in the kidney than those of the other two groups. The expression of vimentin was significantly higher in the MG than in the SOG. The expression of AQP1 mRNA in the lung and kidney, and AQP4 mRNA in the kidney in the MG were all up-regulated compared to that of the SOG.
YBT might regulate water metabolism to reduce lung and kidney edema in SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury.
As we observed that YBT might regulate water metabolism to reduce lung and kidney edema in SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury, further investigation of the underlying molecular mechanisms of YBT in regulating AQP is required to provide experimental evidence for wider clinical usage.