急性排斥反应是影响肝移植术后受者存活的重要因素。Salidroside有各种属性,包括消炎药,抗氧化剂,和保肝性能。本研究旨在探讨红景天苷是否可以预防肝移植后的急性排斥反应,并探讨其相关机制。在肝移植后用他克莫司(1mg/kg/d)或红景天苷(10或20mg/kg/d)预处理7天的大鼠中建立了体内急性排斥模型。此外,使用与红景天苷(1、10、50或100μM)孵育的嗜中性粒细胞进行体外实验。苏木精-伊红染色,末端脱氧核苷酸转移酶dUTP缺口末端标记染色,免疫吸附测定,免疫荧光分析,伊文思蓝染色,进行和western印迹分析以检查红景天苷在体外和体内对NET形成和急性排斥的影响。我们发现,红景天苷治疗减少病理性肝损伤,血清转氨酶水平,和血清IL-1β水平,体内IL-6和TNF-α。HMGB1/TLR-4/MAPK信号通路相关蛋白(HMGB1、TLR-4、p-ERK1/2、p-JNK、p-P38,cleavedcaspase-3,cleavedcaspase-9,Bcl-2,Bax,IL-1β,TNF-α,红景天苷治疗后,IL-6)也降低。体外实验表明,红景天苷降低了脂多糖处理的中性粒细胞释放HMGB1/TLR-4/MAPK信号通路相关蛋白的作用。此外,红景天苷通过调节HMGB1/TLR-4/MAPK信号通路抑制NETosis并保护急性排斥反应。此外,红景天苷联合他克莫司的治疗效果优于其他任何一种单独的治疗方法。总之,红景天苷可通过HMGB1/TLR-4/MAPK信号通路减少中性粒细胞胞外阱的发育,从而预防肝移植后急性肝排斥反应。
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 underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (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, immunofluorescence 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-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside 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.