Cystathionine-gamma-lyase inhibitor attenuates acute lung injury induced by acute pancreatitis in rats

Abstract

Introduction: Acute pancreatitis (AP) is known to induce injuries to extrapancreatic organs. Because respiratory dysfunction is the main cause of death in patients with severe AP, acute pancreatitis-associated lung injury (APALI) is a great challenge for clinicians. This study aimed to investigate the potential role of hydrogen sulfide (H2S) in the pathogenesis of APALI.

Material and methods: Fifty-four SD rats were randomly divided into three groups: the AP group of rats that received injection of sodium deoxycholate into the common bile duct, the control group that underwent a sham operation, and the treatment group made by intraperitoneal injection of propargylglycine (PAG), an inhibitor of cystathionine-γ-lyase (CSE), into rats with AP. Histopathology of the lung was examined and the expression of CSE and TNF-α mRNA in lung tissue was detected by real-time polymerase chain reaction. The H2S level in the serum was detected spectrophotometrically.

Results: The serum concentration of H2S and CSE and TNF-α expression in the lung were increased in AP rats modeled after 3 h and 6 h than in control rats (p < 0.05). Intraperitoneal injection of PAG could reduce the serum concentration of H2S, reduce CSE and TNF-α expression, and alleviate the lung pathology (p < 0.05).

Conclusions: Taken together, our findings suggest that the H2S/CSE system is crucially involved in the pathological process of APALI and represents a novel target for the therapy of APALI.

Keywords: acute pancreatitis associated lung injury; hydrogen sulfide; propargylglycine.

Figure 1

Histopathology of lung tissue of different groups of rats. A – In AP rats, the lung tissue showed a significantly wider alveolar septum, and a large number of infiltrated white blood cells. B – In control rats, the lung tissue was normal. C – After PAG treatment, the pulmonary interstitial edema, alveolar exudation, and bleeding were significantly decreased. Arrows indicate white blood cells. Bar: 100 μM