吴茱萸次碱对大鼠急性肾损伤氧化应激的影响及机制研究

Effects and mechanism of erigeronine on oxidative stress in rats with acute renal injury

目的采用夹闭法制造急性肾损伤大鼠动物模型,研究吴茱萸次碱对大鼠缺血再灌注早期氧化应激损伤的影响及可能机制。方法随机将100只成年雄性大鼠分为5组:假手术组(Sham组)、肾缺血再灌注组(IRI组)、生理盐水组(NS组)、低剂量组(Ru-30组)、高剂量组(Ru-60组)。采用夹闭法建立大鼠急性肾损伤模型,观察吴茱萸次碱预处理后大鼠肾功能及肾组织中丙二醛(MDA)、超氧化物歧化酶(SOD)及血清中一氧化氮(NO)的变化情况,探讨其对肾缺血再灌注早期肾损伤的影响及机制。结果 IRI组与NS组较Sham组血清中尿素氮(BUN)、肌酐(Cr)显著升高(P<0.01),肾脏组织中MDA含量也显著升高(P<0.05),而肾脏组织SOD活性较Sham组显著降低(P<0.05)。与IRI组和NS组比较,Ru-30组和Ru-60组中血清BUN、Cr、NO含量和肾脏组织中MDA含量显著降低而肾脏SOD活性显著升高(P<0.05)。结论吴茱萸次碱具有抗缺血再灌注损伤作用,其可能机制是通过抗脂质过氧化、清除自由基、抗细胞凋亡或阻断JNK/p38 MAPK信号通路途径的激活等原因,从而对肾脏缺血再灌注损伤产生保护作用。

Objective To investigate the effects of Ru on oxidative stress and the underlying mechanisms in rat models of renal isehemia reperfusion injury（ IRI）. Methods Rats were anesthetized with chloral hydrate（ 100 mg/kg） intraperitoneally,and then randomly divided into 5 groups（ n = 20 in each group） as follows： the Sham group,IRI group,Ru-30 group,and Ru-60 group. Blood and kidney samples were obtained for analysis after 48 h of reperfusion. Results The levels of blood BUN and Cr levels increased significantly,while the renal functions impaired severely in the IRI and NS groups,comparing with the Sham group（ P〈0. 01）. In addition,treating with 30 mg/kg and 60 mg/kg Ru evidently decreased renal MDA,serum BUN,Cr and NO levels,but increased renal SOD level,comparing with the IRI and NS groups（ P〈0. 05）. Conclusion This study confirms that rutaecarpin exerts extensive anti-oxidative effects in IRI rat models. The mechanisms could be related to various physiopathological links of IRI. Ru may resist lipid peroxidation,and eliminate free radicals to alleviate renal ischemia reperfusion-induced apoptosis and oxidative stress injury. Therefore,these findings demonstrate that rutaecarpin may be used as a compound to prevent or treat renal IRI.