【作者】 韩菲； 郭沛然； 孙玉凤；

【机构】 河北医科大学第二医院消化内科；

【摘要】 目的:丁基苯酞(恩必普)为治疗脑血管类疾病的临床常用药物。本实验通过应用丁基苯酞对糖尿病肝损伤模型大鼠进行干预,观察氧化应激水平及Nrf2通路变化,探讨氧化应激在糖尿病肝损伤中的作用以及丁基苯酞可能的治疗机制。方法:60只健康雄性SD大鼠,随机分为对照组(Contro1)、糖尿病模型组(DM)、丁基苯酞组(NBP)。于后12周末,分离血清,测定ALT、AST、GLU、TG、TC、HDL、LDL、MDA、T-SOD;PAS染色观察肝脏糖原分布,Fn免疫组化半定量细胞外基质水平;检测肝组织MDA含量、T-SOD活力,Western Blot法检测肝脏Nrf2、HO-1、Catalase的表达及分布情况。结果:1.PAS糖原染色可见正常组大鼠肝细胞胞质内散在紫红色糖原颗粒,分布较均匀,界限清楚,染色深。模型组大鼠糖原颗粒含量明显减少,分布稀疏、不均匀。丁基苯酞组大鼠糖原含量明显增多且分布均匀。2.与对照组相比,模型组、丁基苯酞组大鼠血清ALT、AST、GLU、TC、TG、LDL含量明显升高;与模型组相比,丁基苯酞组大鼠血清以上指标明显降低;模型组、丁基苯酞组大鼠血清HDL明显降低;与模型组相比,丁基苯酞组大鼠血清HDL明显升高。3.与对照组相比,模型组、丁基苯酞组大鼠肝组织MDA及T-SOD含量明显升高;丁基苯酞组大鼠肝组织MDA及T-SOD含量明显降低。4.免疫组化示,同对照组相比,糖尿病组Nrf2在胞核内表达明显增强,丁基苯酞组尤为突出;作为Nrf2下游的两个抗氧化蛋白,丁基苯酞组HO-1、Catalase表达较高。对照组Fn于中央静脉及汇管区少有分布,同期模型组表达较高,丁基苯酞组Fn表达明显减少。Western Blot提示,同对照组相比,模型组和丁基苯酞组肝脏肝脏Nrf2、HO-1、Catalase表达较高;同模型组相比,丁基苯酞组Nrf2、HO-1、Catalase水平明显升高。结论:丁基苯酞可特异激活Nrf2,改善氧化应激,纠正糖脂代谢紊乱,从而减轻糖尿病肝损伤。更多还原

【Abstract】 Objective:Dl-3-n-butylphthalide(NBP) is broadly used on cerebrovascular disorders The study intervened rats with diabetic liver injury by administration of NBP to evaluate oxidative stress and Nrf2-ARE pathway and to explore its theraputic mechanism.Methods:60 male Sprague-Dawley rats were randomly separated into control group,diabetes mellitus group(DM group) and NBP group.The animals were sacrificed after 12 weeks and serum samples were tested for GLU、 TG、 TC、 HDL、 LDL、MDA、 T-SOD.Also,the liver of each animal was excised to observe the histopathological changes and the expression of MDA and SOD.The expressions of FN in liver tissues were analyzed by immunohistochemical staining.The expression of Nrf2,HO-1,Catalase in rat liver tissues were examined by Western Blot.Results:l.Compared with control group,the content of glycogen in model group decreased and maldistribution,while NBP group indicated obviously increased glycogen and distributed well.2.The serum level of ALT ALT,AST,GLU,TC,TG,LDL both in model group and NBP group both had a significantly high level;NBP group had a decreased level compared with model group.The serum level of HDL decreased in model and NBP group in comparison with control group.NBP had a higher level in comparison with model group.3.The content of MDA and T-SOD increased after treating with STZ.NBP group increased in serum and liver compared with model group.4.The content of nuclear nrf2 increased in model and NBP group in comparison with control group,especially in NBP group.The expression of HO-1 and Catalase were detected in three groups and increased especially in NBP group.NBP group showed a decreasing level of Fn in comparison with model group.Western Blot:The expression of nuclear Nrf2 increased in model and NBP group compared with control group.The expression of Nrf2 increased in NBP group in comparison with model group.The levels of anti-oxidant proteins such as HO-1 and Catalase increased in both model and NBP group,especially in NBP group.Conclusions:NBP specifically activated the expression of Nrf2,improved disorder of glucose and lipid metabolism and alleviated diabetic liver injury.更多还原