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已发表论文
探究红景天苷通过抑制大鼠胰腺腺泡细胞中 RIPK1/RIPK3/MLKL 通路介导的坏死性凋亡在缓解急性胰腺炎中的作用
Authors Lin Y , Ma X, Zhang L, Gu H, Fu X, Li P
Received 9 June 2025
Accepted for publication 21 October 2025
Published 27 October 2025 Volume 2025:18 Pages 14857—14869
DOI https://doi.org/10.2147/JIR.S545785
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Professor Ning Quan
Yujie Lin,1 Xiangli Ma,1 Ling Zhang,1 Hao Gu,2 Xu Fu,1 Peiwu Li1
1Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, People’s Republic of China; 2Department of Vascular Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, People’s Republic of China
Correspondence: Peiwu Li, Department of Emergency of The Second Hospital & Clinical Medical School of Lanzhou University, Lanzhou, 730030, People’s Republic of China, Email lipeiw@lzu.edu.cn
Background: Necroptosis, a regulated form of cell death, is a key driver of pancreatic injury in acute pancreatitis (AP). Salidroside (Sal), a natural compound known for its antioxidant properties, was investigated for its potential to alleviate AP by targeting the necroptotic pathway.
Methods: An AP model was induced in Wistar rats via retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into three groups: sham, AP model, and AP + Sal (60 mg/kg). Serum levels of amylase (AMY) and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured, and pancreatic tissue damage was assessed. The involvement of the RIPK1/RIPK3/MLKL pathway and mitochondrial ultrastructure were analyzed by Western blot, immunohistochemistry (IHC), and transmission electron microscopy (TEM). An in vitro AP model was established in AR42J cells using cerulein (100 nM). Cells were pretreated with Sal or Necrostatin-1 (Nec-1), and mitochondrial membrane potential, necroptosis-related protein expression, and p-MLKL subcellular localization were examined.
Results: Sal treatment significantly reduced serum AMY levels (p < 0.01) and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α; all p < 0.05) in AP rats. Histopathological analysis revealed that Sal markedly ameliorated pancreatic tissue edema, inflammatory infiltration, and necrosis (p < 0.01). Western blot analysis showed that Sal significantly inhibited the expression of key necroptosis-related proteins (RIPK1, RIPK3, and p-MLKL) in both pancreatic tissue and AR42J cells (all p < 0.05). IHC and immunofluorescence confirmed that Sal effectively suppressed p-MLKL membrane translocation (p < 0.01). TEM further demonstrated that Sal preserved mitochondrial structural integrity. However, in vitro, the combination of Sal and Nec-1 did not produce a significant additive effect.
Conclusion: Sal alleviates experimental AP by inhibiting necroptosis, likely through targeting the RIPK1/RIPK3/MLKL pathway and preserving mitochondrial function. These findings suggest that Sal is a promising therapeutic candidate for AP treatment.
Keywords: acute pancreatitis, salidroside, necroptosis, RIPK1/RIPK3/MLKL pathway, mitochondrial dysfunction
1Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, People’s Republic of China; 2Department of Vascular Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, People’s Republic of China
Correspondence: Peiwu Li, Department of Emergency of The Second Hospital & Clinical Medical School of Lanzhou University, Lanzhou, 730030, People’s Republic of China, Email lipeiw@lzu.edu.cn
Background: Necroptosis, a regulated form of cell death, is a key driver of pancreatic injury in acute pancreatitis (AP). Salidroside (Sal), a natural compound known for its antioxidant properties, was investigated for its potential to alleviate AP by targeting the necroptotic pathway.
Methods: An AP model was induced in Wistar rats via retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into three groups: sham, AP model, and AP + Sal (60 mg/kg). Serum levels of amylase (AMY) and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured, and pancreatic tissue damage was assessed. The involvement of the RIPK1/RIPK3/MLKL pathway and mitochondrial ultrastructure were analyzed by Western blot, immunohistochemistry (IHC), and transmission electron microscopy (TEM). An in vitro AP model was established in AR42J cells using cerulein (100 nM). Cells were pretreated with Sal or Necrostatin-1 (Nec-1), and mitochondrial membrane potential, necroptosis-related protein expression, and p-MLKL subcellular localization were examined.
Results: Sal treatment significantly reduced serum AMY levels (p < 0.01) and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α; all p < 0.05) in AP rats. Histopathological analysis revealed that Sal markedly ameliorated pancreatic tissue edema, inflammatory infiltration, and necrosis (p < 0.01). Western blot analysis showed that Sal significantly inhibited the expression of key necroptosis-related proteins (RIPK1, RIPK3, and p-MLKL) in both pancreatic tissue and AR42J cells (all p < 0.05). IHC and immunofluorescence confirmed that Sal effectively suppressed p-MLKL membrane translocation (p < 0.01). TEM further demonstrated that Sal preserved mitochondrial structural integrity. However, in vitro, the combination of Sal and Nec-1 did not produce a significant additive effect.
Conclusion: Sal alleviates experimental AP by inhibiting necroptosis, likely through targeting the RIPK1/RIPK3/MLKL pathway and preserving mitochondrial function. These findings suggest that Sal is a promising therapeutic candidate for AP treatment.
Keywords: acute pancreatitis, salidroside, necroptosis, RIPK1/RIPK3/MLKL pathway, mitochondrial dysfunction