基于血小板活化因子研究灯盏花素改善非酒精性脂肪肝病大鼠氧化应激作用

Effects of breviscapine on oxidative stress in rats with non-alcoholic fatty liver disease based on platelet activating factor

目的:构建非酒精性脂肪肝病(NAFLD)大鼠模型,从血小板活化因子(PAF)信号通路探究灯盏花素对其的作用。方法:72只雄性SD大鼠随机分为正常组,模型组,阿司匹林组,灯盏花素低、中和高剂量组,每组12只。高脂高糖喂养12周构建NAFLD模型,治疗4周后处死,观察肝脏病理学,检测肝功能(AST、ALT)、PAF、血小板聚集率、肝脏血脂(DAG、TG、TC)和肝脏氧化应激指标(SOD、MDA、GSH),以及肝脏组织血小板活化因子受体(PAFR)、磷脂酶C(PLC)、p38丝裂原活化蛋白激酶(p38MAPK)和蛋白激酶Cδ(PKCδ)蛋白和mRNA表达情况。结果:与正常组比较,模型组大鼠血清AST、ALT、PAF和血小板聚集率显著升高(P<0.05);与模型组比较,各治疗组显著降低(P<0.05);与正常组比较,模型组大鼠肝脏DAG、TG、TC和MDA显著升高(P<0.05),SOD和GSH显著降低(P<0.05);与模型组比较,各治疗组DAG、TG、TC和MDA降低(P<0.05),SOD和GSH显著升高(P<0.05);HE染色显示正常组肝脏光滑,细胞大小均一,模型组弥漫有大量脂肪空泡,灯盏花素治疗后好转;与正常组比较,模型组大鼠肝脏PAFR、PLC、p38MAPK和PKCδ蛋白及mRNA表达升高(P<0.05),与模型组比较,各治疗组显著降低(P<0.05)。结论:灯盏花素可调节PAF,提高肝脏抗氧化能力,进而保护高脂高糖饮食所带来的肝脏损害。

Objective:To construct non-alcoholic fatty liver disease(NAFLD)rat model,explore the effect of breviscapine on platelet-activating factor(PAF)signaling pathway.Methods:A total of 72 male SD rats were randomly divided into the normal,model,aspirin,breviscapine low-,medium-and high-dose groups,12 rats in each group,a high-fat diet for 12 weeks to construct NAFLD model,they were sacrificed after 4 weeks of treatment.The liver pathology,serum liver function(AST and ALT),PAF,platelet aggregation,liver fat(DAG,TG,and TC)and liver oxidative stress indicators(SOD,MDA,and GSH),as well as the expression of platelet-activating factor receptor(PAFR)were detected,phospholipase C(PLC),p38 mitogen-activated protein(p38 MAPK)and protein kinase Cδ(PKCδ)were detected.Results:Compared with the normal group,the AST,ALT,PAF and platelet aggregation rates in the model group were increased(P<0.05).Compared with the model group,the treatment groups were significantly reduced(P<0.05).Compared with the normal group,the DAG,TG,TC and MDA in the model group were increased(P<0.05),while SOD and GSH were reduced(P<0.05).DAG,TG,TC and MDA in treatment grops were decreased than the model group(P<0.05),while SOD and GSH were increased(P<0.05);HE staining showed that the liver surface in the normal group was smooth,while in the model group was diffuse fat vacuoles,and they were significantly improved after treatment.Compared with the normal group,the expression of PAFR,PLC,p38 MAPK,PKCδprotein and mRNA in the model group were increased(P<0.05);Compared with the model group,the above indicators in treatment groups were reduced(P<0.05).Conclusion:Breviscapine can regulate platelet-activating factor,improve the liver antioxidant capacity thereby protecting liver damage caused by high-fat and high-sugar diet.