Abstract：
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.
摘要：
在重症急性胰腺炎（SAP）中，肠黏膜屏障损伤可引起肠道细菌移位，诱发或加重全身感染。血红素加氧酶-1（HO-1）是一种有效的抗氧化剂和细胞保护剂。本研究旨在探讨HO-1对SAP诱导的SAP大鼠肠屏障损伤的作用及机制。健康成年雄性SD大鼠随机分为假手术组,SAP组,SAP+Hemin集团,和SAP+Znpp组。采用胰胆管逆行注射牛磺胆酸钠(5%)建立大鼠SAP模型。在SAP之前24小时，在选定的组中腹膜内注射Hemin（有效的HO-1激活剂）和Znpp（HO-1的竞争性抑制剂）。每组24小时后收集血清和肠组织样品进行分析。Hemin预处理显著减少全身炎症,肠道氧化应激，并通过增加HO-1的表达而使SAP中的肠上皮凋亡。同时,Hemin预处理消除了对紧密连接蛋白表达的抑制作用，并显着抑制了MLCK/P-MLC信号通路的激活。相反，ZnPP完全逆转了这些作用。我们的研究表明，HO-1表达的上调可减轻SAP的肠粘膜屏障损伤。HO-1对肠的保护作用归因于MLCK/p-MLC信号通路抑制。
