Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats

Abstract

Severe acute pancreatitis (SAP) is initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, leading to self-digestion and inflammatory responses in pancreatic ductal cells, thus giving rise to systemic inflammatory response syndrome (SIRS). The most common and serious SIRS is pancreatitis-associated lung injury, and inflammatory mediators play an important role in its pathogenesis. Bone marrow-derived mesenchymal stem cells (MSCs) are differentiated into alveolar endothelial cells to replace the damaged alveolar endothelial cells and inhibit inflammatory response in the injured lung tissues. In this study, we aimed to investigate the therapeutic effect of bone marrow-derived MSCs in rats with pancreatitis-associated lung injury. Experimental SAP was induced by a retrograde injection of 5% sodium taurocholate into the biliopancreatic duct of 75 male Sprague-Dawley rats, which were divided into the SAP group (n=25), the MSC group (n=25) and the sham-operated group (n=25) to explore the pathology and function of lung tissues and the regulation of inflammatory mediators. Pulmonary edema was estimated by measuring water content in the lung tissues. Pulmonary myeloperoxidase (MPO) activity was detected using spectrophotometry. Serum amylase was detected using the Automatic Biochemistry Analyzer. Tumor necrosis factor-α (TNF-α) and substance P (SP) mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that serum amylase activity was significantly decreased in the MSC group compared to the SAP group. Pulmonary edema was significantly diminished (p<0.05) in the MSC group compared to the SAP group. Typical acute lung injury was observed in the SAP group, and the pathological changes were mild in the MSC group. The expression of TNF-α and SP mRNA in lung tissue was diminished in the MSC group compared to the SAP group. In conclusion, MSC transplantation attenuates pulmonary edema and inflammation, and reduces the mRNA expression of TNF-α and SP in pancreatitis-associated lung injury.

Keywords: mesenchymal stem cells; severe acute pancreatitis; pancreatitis-associated lung injury; substance P; tumor necrosis factor-α.