Protective Effects of Monoacylglycerol Lipase Inhibition in Rats with Severe Acute Pancreatitis and Its Possible Mechanism.

Background and aim: In the context of gastrointestinal diseases, the role of monoacylglycerol lipase (MAGL) is significant. Therefore, the objective of this study was to examine the protective effects of MAGL inhibition using JZL184 in rat models of severe acute pancreatitis (SAP) and to explore its mechanism.

Methods: In this study, a rat model of SAP was established, and the rats were divided into three groups for treatment: the Control group (CON), the SAP group (SAP), and the SAP group treated with JZL184 (JZL184). The serum levels of amylase (AMS), alanine aminotransferase (ALT), creatinine (Cr), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and phosphodiesterase (PDE) were measured using enzyme-linked immunosorbent detection kits. The ascites volume was determined using the cotton ball weighing method. The levels of reactive oxygen species (ROS) were detected using the ROS Kit. Additionally, histological tissue changes were assessed through hematoxylin and eosin staining.

Results: The SAP group showed increased levels of AMS, ALT, Cr, ROS, and ascites volume compared to the CON group. Additionally, the SAP group exhibited congested and edematous lung and pancreatic tissues with inflammation. However, the JZL184 group, when compared to the SAP group, showed decreased levels of AMS, ALT, Cr, and ROS, reduced ascites volume, and significantly reduced lung tissue and pancreatic histopathology scores. In the NO/cGMP/PDE system, compared with the CON group, the levels of NO and PDE in the SAP group were higher and the levels of cGMP were lower. Compared with the SAP group, the JZL184 group decreased NO and PDE levels and increased cGMP levels.

Conclusions: Indeed, the inhibition of MAGL with JZL184 has been found to have a protective effect on rats with SAP. Specifically, it has shown significant improvement in the pathological damage of lung and pancreatic tissues. Furthermore, JZL184 has also exhibited protective effects on the liver and kidney. The mechanism may be related to the effect of JZL184 on the NO/cGMP/ PDE signaling pathway.