目的:研究沙棘多糖提取物对LPS联合D-GalN诱导的肝损伤的保护作用以及对肝脏TLR4,SOCS3蛋白表达的调控。方法:将C57BL/6系雄性小鼠随机分为6组,即空白对照组、模型组、地塞米松阳性对照组、沙棘多糖低、中、高剂量组;沙棘多糖低、中、高剂量组分别以50、100和200 mg/kg沙棘多糖溶液连续灌胃14 d。通过腹腔注射LPS(10μg/kg)和DGalN(700 mg/kg)建立急性肝损伤模型,阳性药物组在建模前腹腔注射地塞米松(10 mg/kg)。建模4 h后采集血清和肝脏组织,检测血清ALT和AST水平,HE染色观察沙棘多糖提取物对肝损伤的影响。Western blot检测TLR4,SOCS3的表达情况。结果:沙棘多糖提取物显著降低了LPS/D-GalN诱导的小鼠血清中ALT和AST水平(P〈0.01,P〈0.05);HE染色观察显示,沙棘多糖明显减轻了肝细胞损伤和炎性细胞浸润。Western blot检测表明,沙棘多糖提取物抑制了LPS/D-GalN诱导的TLR4的表达,但是对SOCS3的表达影响不明显。结论:沙棘多糖提取物有效抑制了LPS/D-GalN诱导的肝损伤,这种保护作用可能是通过抑制TLR4的表达来发挥作用的,而非通过调控SOCS3来实现的。
Objective: To study the protective effects of sea buckthorn polysaccharide extracts on lipopolysaccharide( LPS) /Dgalactosa mine( D-GalN)-induced liver injury in mice and investigate the regulation on hepatic TLR4 and SOCS3 expression. Methods: C57 BL /6 male mice were randomly divided into six groups: control group,model group,dexamethasone positive control group,low,medium and high dose group of sea buckthorn polysaccharide. Mice in the sea buckthorn polysaccharides low,medium and high dose group were gavaged with 50,100 and 200 mg/kg sea buckthorn polysaccharide extracts for 14 days respectively. Acute liver injury model were established by intraperitoneal injection of LPS( 10 μg/kg) and D-GalN( 700 mg/kg). The mice in the dexamethasone positive control group were intraperitoneally injected with dexamethasone( 10 mg/kg) before model establishment. Serum and liver samples were collected after model establishment for 4 h. Serum levels of ALT and AST were detected. Histological changes of liver tissue were observed by HE staining. Hepatic expression of TLR4 and SOCS3 was detected by Western blot. Results: Sea buckthorn polysaccharide significantly inhibited LPS/D-GalN-induced elevation in serum levels of ALT and AST. It also alleviated liver cell injury and inflammatory infiltration. Western blot results showed that sea buckthorn polysaccharide inhibited LPS/D-GalN-induced TLR4 expression. SOCS3 expression was not dramatically influenced by sea buckthorn polysaccharide supplementation. Conclusion: Sea buckthorn polysaccharide protects against LPS/D-GalN-induced liver injury. This protective effects may be achieved by inhibiting the expression of TLR4 but not associated with modulation on SOCS3 expression.