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目的:探讨降脂抗氧化合剂对ApoE基因敲除小鼠(ApoE-/-小鼠)5-脂氧化酶(5-LO)通路表达的影响。方法:采用高脂饲料连续喂养12周ApoE-/-小鼠,建立动脉粥样硬化动物模型,将已经形成动脉粥样硬化的ApoE-/-小鼠分为模型对照组、降脂抗氧化合剂低剂量组、降脂抗氧化合剂高剂量组、阳性药(辛伐他汀)对照组,每组10只。同时选用同遗传背景正常C57BL/6J小鼠10只,作为正常对照组,予饲喂普通饲料。阳性药(辛伐他汀)对照组以0.05 g·kg-1·d-1ig,降脂抗氧化合剂低、高剂量组分别含生药17.41,69.66 g·kg-1·d-1ig,正常对照组及模型对照组分别给予同体积的蒸馏水,连续ig 28 d后,心脏取血用于酶联免疫测定,取腹主动脉,采用HE染色对腹主动脉的形态学改变进行观察;提取腹主动脉RNA,进行RT-PCR检测5-LO基因的表达量;同时采用ELISA方法检测血清中白三烯B4(LTB4)及白三烯D4(LTD4)的蛋白含量。结果:与正常组比较,模型组的动脉硬化病变、组织5-LO、血清LTB4及LTD4水平都有明显加重或升高(P<0.01)。与模型组比较,高剂量的降脂抗氧化合剂较低剂量的降脂抗氧化合剂可以更显著下调5-LO的基因表达量(P<0.01),病理切片HE染色显示给药降脂抗氧化合剂后,高剂量给药组血管的组织形态较模型组有明显改变,和阳性药组结果类似,显示出药物对动脉粥样硬化具有较好的治疗效果;血清ELISA法结果显示高剂量的降脂抗氧化合剂可以显著降低血液LTB4及LTD4水平,与模型组间比较差异显著(P<0.01)。结论:降脂抗氧化合剂可降低组织5-LO的水平,改善动脉粥样硬化血管组织形态,减少脂质沉积,还可以降低血清LTB4及LTD4水平,改善炎症,达到治疗动脉粥样硬化的目的。
Objective: To investigate the effect of lipid-lowering anti-oxidant on 5-lipoxygenase (5-LO) pathway in ApoE knockout mice (ApoE - / - mice). Methods: The animal models of atherosclerosis were established by continuous feeding of ApoE - / - mice with high fat diet for 12 weeks. ApoE - / - mice that had formed atherosclerosis were divided into model control group, lipid - Low-dose group, high-dose lipid-lowering antioxidant group, positive drug (simvastatin) control group, 10 in each group. Meanwhile, 10 C57BL / 6J mice with the same genetic background were selected as normal control group and fed with normal feed. Positive control (simvastatin) control group with 0.05 g · kg-1 · d-1ig, lipid-lowering anti-oxidant low and high dose groups were crude drug 17.41,69.66 g · kg-1 · d-1ig, normal control group And control group were given the same volume of distilled water, continuous ig 28 d, the heart blood for enzyme-linked immunoassay, take the abdominal aorta, the morphology of the abdominal aorta were observed by HE staining; extract the abdominal aorta RNA was used to detect the expression of 5-LO gene by RT-PCR. Meanwhile, the protein contents of leukotriene B4 (LTB4) and leukotriene D4 (LTD4) in serum were detected by ELISA. Results: Compared with the normal group, the levels of 5-LO, LTB4 and LTD4 in the model group were significantly increased or increased (P <0.01). Compared with the model group, high-dose lipid-lowering anti-oxidants and lower doses of lipid-lowering anti-oxidant agents can significantly reduce the gene expression of 5-LO (P <0.01), pathological sections of HE staining showed that lipid- Compared with the model group, the histomorphology of vascular in the high-dose group changed obviously after the mixture, which shows that the drug has a good therapeutic effect on atherosclerosis. The serum ELISA results showed that the high-dose Lipid anti-oxidant can significantly reduce the level of blood LTB4 and LTD4 compared with the model group (P <0.01). Conclusion: The lipid-lowering anti-oxidant can reduce the level of 5-LO tissue, improve the morphology of atherosclerotic vascular tissue, reduce lipid deposition, but also reduce the level of serum LTB4 and LTD4, improve inflammation and achieve the purpose of treating atherosclerosis .