Intensive care research最新文献

Heme Oxygenase-1 Protected Against Severe Acute Pancreatitis by Inhibiting Inflammatory Response 血红素加氧酶-1通过抑制炎症反应预防重症急性胰腺炎

Intensive care research Pub Date : 2024-10-16 DOI: 10.1007/s44231-024-00074-7

Yuansong Sun, Jinwei Qi, Tingting Yao, Chunlin Yin, Min Yang, Weiwei Ge

{"title":"Heme Oxygenase-1 Protected Against Severe Acute Pancreatitis by Inhibiting Inflammatory Response","authors":"Yuansong Sun, Jinwei Qi, Tingting Yao, Chunlin Yin, Min Yang, Weiwei Ge","doi":"10.1007/s44231-024-00074-7","DOIUrl":"https://doi.org/10.1007/s44231-024-00074-7","url":null,"abstract":"Abstract Background Activation of NLPR3 inflammasome promotes the maturation and secretion of IL-1β and IL-18, leading to a series of inflammatory reactions, while inhibition of NLRP3 inflammasome alleviates the severity of Severe Acute Pancreatitis (SAP). An inducible enzyme responsible for heme decomposition, heme oxygenase-1 (HO-1), has anti-inflammatory, antioxidant, and anti-proliferative effects. HO-1 activity profoundly affects the host ability to forbear infection by reducing tissue damage or affecting resistance and increasing the capacity to pathogen load. We postulated that hemin, a strong HO-1 inducer, could decrease NLRP3 inflammasome activation, which would alleviate the severity of SAP and acute lung injury caused by pancreatitis. Methods By administering intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS), the SAP rat model was created. Then, the SAP rats were pretreated with Hemin or zinc protoporphyrin IX (Znpp, a HO-1 inhibitor) to stimulate or inhibit the HO-1 enzyme respectively, and the effects and mechanisms were investigated. Results The pancreas and lung tissue of the SAP rats suffered considerable pathological damage after Cae and LPS injection, with significant increases of amylase, lipase, IL-1β and IL-18 levels in the serum. Hemin pretreatment decreased IL-1β and IL-18 release in the serum and prevented pancreatic and pulmonary damage. Hemin dramatically reduced oxidative stress, downregulated the expression of NLRP3, ASC, and Caspase-1, and elevated HO-1 expression. On the contrary, there were no discernible changes between the SAP control and Znpp treated groups. Conclusion These results showed that hemin prevented Cae and LPS-induced lung and pancreatic injury through suppression of the inflammatory response. The impact of hemin on the activity of the NLRP3 inflammasome was depending critically on HO-1 activity. The protective role and mechanism HO-1 against the acute and severe inflammatory responses may provide a novel and effective therapeutic approach for SAP treatment.","PeriodicalId":73403,"journal":{"name":"Intensive care research","volume":"5 1-2","pages":"49-57"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s44231-024-00074-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147886269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}