四氢生物蝶呤对大鼠低密度脂蛋白氧化修饰的作用及其机制探讨  

Effect of low density lipoprotein oxidizing in hyperlipidemia rats after treating with tetrahydrobiopterin

作　　者：朱宝亮[1] 赵颖[2] 刘景[3] 葛凤[1] 刘树玲[3] 王俊杰[1] 刘梅芳[1] 颜红[1] 

机构地区：[1]济宁医学院生理学教研室,山东日照276826 [2]济宁医学院生化教研室,山东日照276826 [3]济宁医学院药学院,山东日照276826

出　　处：《中国应用生理学杂志》2012年第5期449-453,共5页Chinese Journal of Applied Physiology

基　　金：山东省自然科学基金资助项目(ZR2009CL009)

摘　　要：目的:探讨四氢生物蝶呤(BH4)治疗高脂血症(HL)大鼠对低密度脂蛋白(LDL)氧化修饰作用及其机制。方法:选用8周龄雄性Wistar大鼠54只,随机分为对照组(普通饮食)、高脂饮食组(HL组)和高脂饮食并腹腔注射BH4组(HL+BH4组)(n=18)。于实验前、实验8周和16周时每组各杀死6只大鼠测定血脂和血清BH4水平,测定主动脉血管活性氧(ROS)、脂质过氧化代谢终产物丙二醛(MDA)和LDL氧化修饰水平。结果:至实验8周和16周时,HL组和HL+BH4组血脂水平较对照组均明显升高(P<0.01),但HL组和HL+BH4组之间无明显差异(P>0.05);ROS和MDA明显降低(P<0.01);HL+BH4组较对照组和HL组BH4水平均明显升高(P<0.01);与对照组相比,HL组大鼠主动脉匀浆中BH4含量明显降低(P<0.01),但总喋呤水平(TB=BH4+BH2+B)无明显差异(P>0.05);HL组大鼠血清硫代巴比妥酸反应物(TBARS)生成量随周龄的增加有逐渐升高的趋势,而HL+BH4组大鼠血清TBARS生成量较HL组明显降低(P<0.01)。结论:BH4可以减轻LDL氧化修饰,其机制可能与纠正NOS脱偶联、ROS生成减少及LDL脂质过氧化降低有关。Objective： To explore the oxidative modification effect and its mechanism of low density lipoprotein（LDL） in huperlipidemia（HL） rats after treating with tetrahydrobiopterin（BH4）.Methods： Fifty four 8-week-old male Wistar rats were used,these 54 rats were randomly divided into control group,high fat diet group（HL group）,high fat diet and injected BH4 group（HL＋BH4 group）,and 18 in each group.The BH4 levels of blood fats and blood serum and its metabolites,the aortic reactive oxygen species,the end product malondialdehyde（MDA） and the LDL oxidation level were all determined by killing 6 experimental rats in each group at the first 8,16,and 24 weeks of age respectively.Results： Treating with BH4 after 8 and 16 weeks,there was no significant difference in serum lipids among three groups（P〉0.05）;but ROS and MDA decreased significantly（P〈0.01）;compared with control and HL groups,the BH4 level of HL＋BH4 group increased a lot（P〈0.01）;compared with control group,the BH4 content reduced obviously in aortic homogenate of HL group（P〈0.01）,but the total petrin levels（TB=BH4＋BH2＋B） had no significant difference（P〉0.05）;the serum TBARS formation increased gradually with the increase of week-ages,but compared with HL group,the serum TBARS formation of HL＋BH4 group reduced significantly（P〈0.01）.Conclusion： Treating with BH4 can reduced the LDL oxidation,the mechanism may be related to the correct of NOS uncoupling,the reduce of ROS generation and the decrease of LDL lipid peroxidation.

关 键 词：四氢生物蝶呤 高脂血症 动脉 低密度脂蛋白 氧化修饰 

分 类 号：R587[医药卫生—内分泌]