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SAK-HV灌胃给药对高脂大鼠降脂效果的影响
引用本文:黄志广,付文亮,景浩然,龙民慧,甘向东,徐东刚.SAK-HV灌胃给药对高脂大鼠降脂效果的影响[J].华南师范大学学报(自然科学版),2016,48(3):115-121.
作者姓名:黄志广  付文亮  景浩然  龙民慧  甘向东  徐东刚
作者单位:1.(1.广西医科大学,南宁530021;
基金项目:国家科技重大专项新药创制项目(2012ZX09102301-017) ;十二五国家重大新药创制生物技术大平台项目(2012ZX09301003-001-005-026)
摘    要:〖JP2〗研究重组蛋白SAK-HV口服给药对高脂模型大鼠血脂水平及氧化应激指标的影响,并对其降低胆固醇机制进行初步探讨.高脂饲料喂养雄性Wistar大鼠10周建立高脂模型,将成模大鼠按体质量随机分为:模型组、溶剂对照(碳酸氢钠)组、给药(SAK-HV)组及阳性对照(他汀)组.口服给药6周,分别检测血清中甘油三酯和总胆固醇含量、肝脏脂肪沉积情况、小肠〖WTBX〗Npc1l1及肝脏Abcg5/Abcg8〖WTBZ〗的mRNA及蛋白表达水平、主动脉ROS含量、血清SOD活性及MDA含量.检测结果显示,与模型组大鼠相比,SAK-HV组大鼠血清总胆固醇和甘油三酯显著降低;肝脏脂肪沉积减少,小肠中NPC1L1的表达显著低下降,同时肝脏ABCG5/ABCG8〖WTBZ〗的表达显著升高;大鼠主动脉ROS含量显著降低,血清SOD活性显著升高,而血清MDA含量显著降低.结果表明SAK-HV口服给药可通过抑制小肠对胆固醇的吸收,〖JP〗增强肝脏对胆固醇的外排作用降低血脂,同时它可降低机体氧化应激水平,因此有望成为治疗高脂血症的候补药物.

关 键 词:SAK-HV    高脂血症    口服给药    胆固醇转运    氧化应激
收稿时间:2015-09-20

Effect of SAK-HV on Reducing Lipid in Hyperlipidemic Rats by Gavage
Institution:1.(1.Guangxi Medical University,Nanning 530021,China;2.2.Institute of Basic Medical Sciences,the Academy of Military Medical Sciences,Beijing 100850,China)
Abstract:This article is to assess the influence of SAK-HV given by gavage on blood lipid and oxidative stress in hyperlipidemia model rats and to investigate the possible mechanism of lowering cholesterol. Male Wistar rats were fed by high-fat diet for 10 weeks to build hyperlipidemia model rats. Then the model rats were randomly assigned to model group, NaHCO3 group, treatment (SAK-HV) group and positire control (atorvastatin) group by body weight and administrated with drugs perorally. 6 weeks later, all rats were anesthetized. Serum, aortas, intestines and livers were separated and analyzed. Data showed that compared to model group, the level of triglyceride and total cholesterol in serum of SAK-HV group were significantly reduced; fat deposition in liver was improved; the expression of NPC1L1 in intestine was inhibited and the expression of ABCG5/ABCG8 in liver was enhanced; the content of ROS in aorta was significantly reduced; the activity of SOD in serum was significantly improved; the content of MDA in serum was significantly decreased. These results demonstrated that SAK-HV could reduce the content of blood lipid, the level of body oxidative stress and the total cholesterol via inhibiting cholesterol intake in intestine and enhancing the excretion of cholesterol in liver. SAK-HV may be a promising candidate drug against hyperlipemia.
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