| First Author | Huang W | Year | 2024 |
| Journal | Int Immunopharmacol | Volume | 143 |
| Issue | Pt 1 | Pages | 113306 |
| PubMed ID | 39405939 | Mgi Jnum | J:358459 |
| Mgi Id | MGI:7781130 | Doi | 10.1016/j.intimp.2024.113306 |
| Citation | Huang W, et al. (2024) Ulinastatin attenuates renal ischemia-reperfusion injury by inhibiting NLRP3 inflammasome-triggered pyroptosis. Int Immunopharmacol 143(Pt 1):113306 |
| abstractText | Systemic inflammation is involved in developing acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urinary trypsin inhibitor (UTI), has various anti-inflammatory effects. Our previous data displayed that UTI administration during CPB played a protective role in reducing the risk of AKI after cardiac surgery; however, its role in AKI pathogenesis remains unknown. In this study, UTI effectively decreased the expression levels of inflammatory factors, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and interleukin (IL)-18, in patients with CPB. Moreover, the proportion of patients with postoperative AKI decreased significantly. Experimental AKI was induced by 35 min of ischemia, followed by 48 h of reperfusion.The results showed that the preoperative administration of UTI reduced inflammatory cell infiltration and decreased the levels of pro-inflammatory cytokines, including IL-6, IL-18, and TNFalpha. Meanwhile, UTI inhibited apoptosis, reduced mitochondrial reactive oxygen species production. We further revealed that UTI could inhibit NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation by increasing the expression of nuclear factor-kappaB (IkappaB) kinase-alpha (IKKalpha) interacting with apoptosis-associated speck-like protein containing CARD (ASC) to alleviate kidney damage. These findings provide evidence of the renoprotective role of UTI in cardiac surgery-associated (CSA)-AKI, which is associated with the inhibition of NLRP3 inflammasome activation by upregulating IKKalpha. |
