Study on the inhibitory effect of ulinastatin on caspase-1-dependent pyroptosis in acinar cells of acute pancreatitis

Abstract

Objectives Pyroptosis, a special kind of cell death, is generally believed to aggravate the inflammatory response. It has been found that the acinar cell pyroptosis exits in the course of pancreatitis. Ulinastatin has the function of inhibiting the release of inflammatory mediators, thereby reducing the inflammatory reaction, which suggests that ulinastatin has potential inhibitory effect on pyroptosis. The aim of this study is to investigate the effect of ulinastatin on caspase-1-dependent acinar cell pyroptosis in acute pancreatitis. Methods Acute pancreatitis model was established by intraperitoneal injection of L-arginine. Rats in ulinastatin group were injected with ulinastatin intravenously after successful modeling. The pancreatic tissues of rats were subjected to pathological examination and detection of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Serum samples were also collected for measurement of IL-1β, IL-18, amylase, and lipase. Results Slight pathological damage of pancreas was observed in the pancreatitis and the ulinastatin group. Compared with the blank control group ( p < .05), the protein levels of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18 were significantly increased in pancreatitis group but decreased in ulinastatin group ( p < .05). The positive reaction of caspase-1 in pancreatitis group was significantly higher than that in the blank control group ( p < .05). After administration of ulinastatin, the positive reaction of caspase-1 was significantly lower than that in pancreatitis group ( p < .05). As for the levels of serum IL-1β and IL-18, they were significantly higher in pancreatitis group than those in the blank control group ( p < .05). Administration of ulinastatin significantly decreased the serum levels of IL-1β and IL-18 ( p < .05). And the serum amylase and lipase levels elevated in pancreatitis group, while significantly inhibited by ulinastatin ( p < .05). Conclusions The results showed that the onset of acute pancreatitis was accompanied by obvious acinar cell pyroptosis. Ulinastatin could inhibit caspase-1-dependent acinar cell pyroptosis in acute pancreatitis.