Elevation of HO-1 expression protects the intestinal mucosal barrier in severe acute pancreatitis via inhibition of the MLCK/p-MLC signaling pathway

• Published in: Experimental cell research Vol. 424; no. 2; p. 113508
• Main Authors: Zhang, Jingyin, Jiang, Yingjian, Li, Hongbo, Wang, Jiang, Li, Chang, Zhang, Dianliang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2023
• Subjects: Acute Disease; Animals; Apoptosis; Heme Oxygenase-1 - metabolism; Hemin - pharmacology; HO-1; Intestinal barrier barrier; Intestinal Mucosa - metabolism; Male; Myosin light chain kinase; Oxidative stress; Pancreatitis - chemically induced; Pancreatitis - drug therapy; Pancreatitis - metabolism; Rats; Rats, Sprague-Dawley; Severe acute pancreatitis; Signal Transduction; Oxidative stress; Intestinal barrier barrier; HO-1; Severe acute pancreatitis; Myosin light chain kinase; Apoptosis
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2023.113508

In severe acute pancreatitis (SAP), intestinal mucosal barrier damage can cause intestinal bacterial translocation and induce or aggravate systemic infections. Heme oxygenase-1 (HO-1) is a validated antioxidant and cytoprotective agent. This research aimed to investigate the effect and mechanism of HO-1 on SAP-induced intestinal barrier damage in SAP rats. Healthy adult male Sprague-Dawley rats were randomly separated into the sham-operated group, SAP group, SAP + Hemin group, and SAP + Znpp group. The rat model of SAP was established by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. Hemin (a potent HO-1 activator) and Znpp (a competitive inhibitor of HO-1) were injected intraperitoneally in the selected groups 24 h before SAP. Serum and intestinal tissue samples were collected for analysis after 24 h in each group. Hemin pretreatment significantly reduced systemic inflammation, intestinal oxidative stress, and intestinal epithelial apoptosis in SAP by increasing HO-1 expression. Meanwhile, pretreatment with Hemin abolished the inhibitory effect on the expression of the tight junction proteins and significantly inhibited the activation of the MLCK/P-MLC signaling pathway. Conversely, ZnPP completely reversed these effects. Our study indicates that upregulation of HO-1 expression attenuates the intestinal mucosal barrier damage in SAP. The protective effect of HO-1 on the intestine is attributed to MLCK/p-MLC signaling pathway inhibition.