首页|Salidroside ameliorates acute liver transplantation rejection in rats by inhibiting neutrophil extracellular trap formation
Salidroside ameliorates acute liver transplantation rejection in rats by inhibiting neutrophil extracellular trap formation
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Acute rejection is an important factor affecting the survival of recipients after liver transplantation.Salidroside has various properties,including anti-inflammatory,antioxidant,and hepatoprotective properties.This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the under-lying mechanisms involved.An in vivo acute rejection model is established in rats that are pretreated with tacro-limus(1 mg/kg/d)or salidroside(10 or 20 mg/kg/d)for seven days after liver transplantation.In addition,an in vitro experiment is performed using neutrophils incubated with salidroside(1,10,50 or 100 μM).Hematoxylin-eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling staining,immunosorbent assays,im-munofluorescence analysis,Evans blue staining,and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo.We find that Salidroside treatment reduces pathological liver damage,serum aminotransferase level,and serum levels of IL-1β,IL-6,and TNF-α in vivo.The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway(HMGB1,TLR-4,p-ERK1/2,p-JNK,p-P38,cleaved caspase-3,cleaved caspase-9,Bcl-2,Bax,IL-1β,TNF-α,and IL-6)are also decreased after salidroside treatment.In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-as-sociated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside.Moreover,sali-droside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway.Furthermore,salidroside combined with tacrolimus has a better effect than either of the other treatments alone.In summary,salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.
Xiaoyan Qin、Han Wang、Qi Li、Dingheng Hu、Liangxu Wang、Baoyong Zhou、Rui Liao、Yanyao Liu
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Department of Hepatobiliary Surgery,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400042,China
Department of General Surgery and Trauma Surgery,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Structural Birth Defect and Reconstruction,Chongqing 400014,China
国家自然科学基金中国博士后科学基金Chongqing Postdoctoral Science Foundation
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