北五味子三萜诱导HO-1对酒精性氧化损伤的保护作用及机制研究

The endogenous antioxidant system mediated and activated by exogenous antioxidant is crucial for the protection of alcoholic oxidative damage.However,classic antioxidants medication plays little role on preventing ethanol-induced oxidative damage,these research outcomes have not been taken into consideration for practical application owing to potential oxidative toxicity and the safety and efficiency of gene transfection. The research will take full advantage of amplify antioxidant effect and exem extensive livercare activity from the triterpene compounds from Schisandra chinensis (Turcz) Baill,that the antioxidants might just by virtue of its induction on HO-1,preliminary tests have shown on the distinct protective function of the triterpene compounds from Schisandra chinensis (Turcz) Baill on antioxidant system of mice after acute alcohol exposure, based on above results we decide to use animal models and molecular and cellular biology means, and carry out the following research: 1）we assayed the serum,iver,kidney,heart antioxidant system,as well as seruln lipid level of rats treated with different dose of ethanol for different endurance.The effect of the triterpene compounds from Schisandra chinensis (Turcz) Baill on ethanol-fed rats with laigh dose will been also investigated in the present part and assure the distinct livercare activity of the triterpene compounds from Schisandra chinensis (Turcz) Baill. 2）Additionally,Enzymatic and biochemical assay,reverse transcriptase-ploymerase chain reaction(RT-PCR),flow cytometry(FCM),western blot,uhramicropathology and etc will be employed in the present study.Hepatic structure and function,antioxidant system of hepatic mitochondria and microsomes,and mRNA,protein expression and enzymatic activity of hepatic HO-1 are being researched after chronic alcohol administration and the triterpene compounds from Schisandra chinensis (Turcz) Baill pretreatment for rats. The research will activate the activity of HO-1 by the triterpene compounds from Schisandra chinensis (Turcz) Baill. The research is useful exploration for similar preventive mechanism of the triterpene compounds on alcoholic liver damage by inducing the expression of HO-1.

内源性抗氧化系统的HO-1（I型血红素氧化酶）的激活,对酒精性氧化损伤的保护具有重要意义。传统孤立地依靠抗氧化剂,具有潜在的过氧化毒性,安全和效率方面也存在问题,难以实际应用,本研究拟利用北五味子三萜协同增效的抗氧化效应及护肝效应,在对小鼠急性酒精暴露后氧化损伤具有明显保护作用的基础上:1）利用动物模型,以灌胃方式使大鼠长时间摄入高、中、低剂量酒精后，揭示血清、肝、心、肾器官中抗氧化系统和脂质水平变化规律，证明北五味子三萜的保护效应；2）采用酶学与生化分析手段,并借助于RT-PCR、流式细胞术、Western Blot等方法,揭示高剂量酒精摄入后,大鼠肝脏结构与功能、肝线粒体与微粒体氧化-抗氧化系统、CYP2El活性及肝HO-1 mRNA及蛋白表达与酶活性的变化规律,确定不同剂量北五味子三萜的干预效果。该研究对探索北五味子三萜诱导HO-1对酒精性氧化损伤的保护作用及机制研究具有重要意义。

利用北五味子三萜协同增效的抗氧化效应及护肝效应，在对小鼠急性酒精暴露后氧化损伤具有明显保护作用的基础上:利用动物模型,以灌胃方式使大鼠长时间摄入高、中、低剂量酒精后，揭示血清、肝、心、肾器官中抗氧化系统和脂质水平变化规律，证明北五味子三萜的保护效应；采用酶学与生化分析手段,并借助于RT-PCR、流式细胞术、Western Blot等方法,揭示高剂量酒精摄入后,大鼠肝脏结构与功能、肝线粒体与微粒体氧化-抗氧化系统、CYP2El活性及肝HO-1 mRNA及蛋白表达与酶活性的变化规律,确定不同剂量北五味子三萜的干预效果。实验结果表明：北五味子三萜能够缓解乙醇代谢引发的脂质过氧化作用，清除氧自由基，保护肝细胞及细胞器的功能和结构；能够调控乙醇代谢中关键酶，尤其是CYP2E1的表达，从而减少ROS的生成，减轻对肝脏造成的氧化损伤；此外还能够诱导HO-1的表达，激活其被乙醇抑制的抗氧化作用，将CYP2E1作为底物降解从而降低其活力，增强机体的抗氧化能力，进而改善酒精摄入造成的氧化损伤，对其干预急性和慢性酒精性氧化损伤的效果及作用机制进行深入研究，为北五味子的产业化开发奠定基础。