复方冬虫夏草口服液对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响
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篇名: 复方冬虫夏草口服液对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响
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摘要: 目的:观察复方冬虫夏草口服液对载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化(AS)的影响,并探讨其作用机制。方法:将45只雄性ApoE-/-小鼠随机分为模型组(生理盐水)、阳性对照组(阿托伐他汀,5 mg/kg)和复方冬虫夏草口服液低、中、高剂量组(0.4、1.2、3.6 g/kg,以生药量计),每组9只;另取9只雄性C57BL/6J小鼠作为空白对照组(生理盐水)。除空白对照组小鼠给予普通饲料外,其余各组小鼠均给予高脂饲料以复制AS模型,并于造模同时每天灌胃给药1次,连续8周。末次给药后,分离血清,检测各组小鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;分离胸主动脉及主动脉窦,以油红O染色,检测胸主动脉斑块损伤面积比(即胸主动脉斑块面积与胸主动脉总面积的比值)和主动脉窦脂质损伤面积比(即主动脉窦脂质沉积面积与主动脉窦管腔总面积的比值);采用免疫组化法测定主动脉窦巨噬细胞表达量(即巨噬细胞阳性表达面积与斑块面积的比值)。结果:与空白对照组比较,模型组小鼠血清TC、TG、LDL-C水平显著升高,HDL-C水平显著下降(P<0.01);胸主动脉斑块形成明显,主动脉窦脂质沉积明显增多,其斑块损伤面积比和脂质损伤面积比均显著升高(P<0.01);主动脉窦巨噬细胞阳性表达明显增加,其表达量显著升高(P<0.01)。与模型组比较,各给药组小鼠血清TC、TG、LDL-C水平均显著降低,HDL-C水平均显著升高(P<0.05或P<0.01);胸主动脉斑块面积及主动脉窦脂质沉积明显减少,其斑块损伤面积比和脂质损伤面积比均显著下降(P<0.05或P<0.01);主动脉窦巨噬细胞浸润明显减少,其表达量显著下降(P<0.05或P<0.01)。结论:复方冬虫夏草口服液可抑制AS斑块形成,其机制可能与降低血清TC、TG、LDL-C水平,缩小胸主动脉斑块面积,减少主动脉窦脂质沉积和巨噬细胞浸润有关。
ABSTRACT: OBJECTIVE: To observe the effects of Compound dongchong xiacao oral liquid on atherosclerosis (AS) in ApoE knock-out (ApoE-/-) mice, and to investigate its mechanism. METHODS: Totally of 45 male ApoE-/- mice were randomly divided into model group (normal saline), positive group (atorvastatin, 5 mg/kg) and Compound dongchong xiacao oral liquid low-dose, medium-dose and high-dose groups(0.4, 1.2, 3.6 g/kg,by crude drug), with 9 mice in each group. Another 9 male C57BL/6J mice were included in blank control group (normal saline). Except blank control group was given common diet, other groups were given high lipid diet to induce AS model and given relevant medicine intragastrically once a day, for consecutive 8 weeks. After last medication, serum was isolated, and the levels of TC, TG, LDL-C and HDL-C were determined. Thoracic aorta and aortic sinus were separated and then stained with oil red O. The ratio of thoracic aortic plaque area (i.e. the ratio of thoracic aortic plaque area to total thoracic aorta area) and the ratio of aortic sinus lipid lesion area (i.e. the ratio of aortic sinus lipid deposition to total area of aortic sinus lumen) were determined. The expression of aortic sinus macrophage (i.e. the ratio of positive expression area of macrophage in plaque area) was determined by immunohistochemical method. RESULTS: Compared with blank control group, the serum levels of TC, TG and LDL-C were increased significantly in model group, while the level of HDL-C was decreased significantly (P<0.01). There were obvious plaque in thoracic aorta and obvious increase of sinus lipid deposition in aortic sinus; the ratio of aortic plaque area and the ratio of aortic sinus lipid lesion area were all increased significantly (P<0.01). The positive expression of aortic sinus macrophage was increased significantly, and its amount was also increased significantly (P<0.01). Compared with model group, the serum levels of TC, TG and LDL-C in administration groups were all decreased significantly, while the level of HDL-C was increased significantly (P<0.05 or P<0.01). The plaque area in thoracic aorta and sinus lipid deposition in aortic sinus were decreased, and the ratio of aortic plaque area and the ratio of aortic sinus lipid lesion area were also decreased significantly (P<0.05 or P<0.01). The macrophage infiltration of aortic sinus was decreased significantly, and its amount was also decreased significantly (P<0.05 or P<0.01). CONCLUSIONS: Compound dongchong xiacao oral liquid can inhibit the generation of AS plaque, the mechanism of which may be associated with the decrease of TC, TG and LDL-C levels in serum, the decrease of thoracic aorta plaque area, the reduce of aortic sinus lipid deposition and the macrophage infiltration.
期刊: 2018年第29卷第14期
作者: 胡抗远,王全兴,鲍蕾蕾,曹志伟,卞俊
AUTHORS: HU Kangyuan,WANG Quanxing,BAO Leilei,CAO Zhiwei, BIAN Jun
关键字: 复方冬虫夏草口服液;载脂蛋白E基因敲除小鼠;动脉粥样硬化;血脂;斑块;脂质沉积;巨噬细胞
KEYWORDS: Compound dongchong xiacao oral liquid; ApoE knock-out mice; Atherosclerosis; Blood lipid; Plaque; Lipid deposition; Macrophage
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