中国普通外科杂志2025，Vol.34Issue(3)：506-515,10.DOI:10.7659/j.issn.1005-6947.240419
乌司他丁抑制TLR4/NF-κB通路介导的炎症反应改善急性胰腺炎相关肠功能障碍
Ulinastatin Inhibits TLR4/NF-κB pathway-mediated inflammatory response to improve acute pancreatitis-associated intestinal dysfunction
摘要
Abstract
Background and Aims:Acute pancreatitis(AP)accompanied by intestinal injury and intestinal barrier dysfunction can significantly worsen AP prognosis.Currently,there is no effective clinical treatment for AP-related intestinal dysfunction.Ulinastatin(UTI)is a conventional drug used for AP treatment due to its ability to inhibit trypsin activity and exert anti-inflammatory effects.However,whether UTI directly improves AP-related intestinal injury remains unclear.Therefore,this study was conducted to investigate the therapeutic effects and potential mechanisms of UTI in AP-related intestinal dysfunction. Methods:Thirty rats were equally randomized into three groups and received intraperitoneal injections of PBS(control group),20%L-arginine(AP group),or 20%L-arginine+UTI(UTI group).Tail vein blood samples were collected at 0,24,and 48 h after the initial injection of L-arginine(or PBS),and the rats were euthanized after the final blood collection to obtain pancreatic and terminal ileum tissues.Serum levels of amylase,lipase,intestinal fatty acid-binding protein(I-FABP),and diamine oxidase(DAO)were measured using ELISA.Histopathological examinations of the pancreas and terminal ileum were conducted.Western blot was used to detect the protein expression levels of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),interleukin 1β(IL-1β),and interleukin 10(IL-10)in terminal ileum tissue.Western blot and qRT-PCR were used to assess the protein and mRNA expression levels of Toll-like receptor 4(TLR4)and nuclear factor κB(NF-κB)p-p65 in the terminal ileum. Results:Compared with the control group,both the AP and UTI groups exhibited significant AP changes(elevated serum amylase and lipase levels,pancreatic histopathological damage)and AP-related intestinal injury(decreased I-FABP and DAO levels,ileal histopathological damage).However,these alterations were significantly less severe in the UTI group compared to the AP group(all P<0.01).Compared with the control group,both the AP and UTI groups showed significantly increased protein expression of pro-inflammatory factors(TNF-α,IL-1β,IL-6)and the anti-inflammatory factor IL-10 in the ileal tissue;however,the UTI group exhibited significantly lower levels of pro-inflammatory factors and higher levels of IL-10 compared to the AP group(all P<0.01).Additionally,compared with the control group,both the AP and UTI groups displayed significant upregulation of TLR4 and NF-κB p-p65 protein and mRNA expressions in ileal tissue,but the upregulations were significantly lower in the UTI group compared to the AP group(all P<0.01). Conclusion:UTI can inhibit the activation of the TLR4/NF-κB signaling pathway in the ileal tissue of AP rats,thereby reducing pro-inflammatory cytokine levels and increasing anti-inflammatory cytokine levels.Therefore,in addition to its anti-pancreatitis effects,UTI may have a direct therapeutic effect on AP-related intestinal dysfunction.关键词
胰腺炎/肠衰竭/乌司他丁/全身炎症反应综合征Key words
Pancreatitis/Intestinal Failure/Ulinastatin/Systemic Inflammatory Response Syndrome分类
医药卫生引用本文复制引用
张思琦,高明,王琪..乌司他丁抑制TLR4/NF-κB通路介导的炎症反应改善急性胰腺炎相关肠功能障碍[J].中国普通外科杂志,2025,34(3):506-515,10.基金项目
安徽医科大学校科研基金资助项目(2023xkj036). （2023xkj036）
