兰州大学机构库 >学院待认领
蛋氨酸负荷对去卵巢大鼠主动脉病变的影响及叶酸、NAC的干预作用
Alternative TitleThe influence of methionine overload on artery lesions in ovariectomized rats and the intervene effect of folic acid、NAC
田盼丽
Thesis Advisor汤旭磊
2009-05-31
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword去卵巢 蛋氨酸 同型半胱氨酸 动脉粥样硬化 氧化应激 单核细胞趋化蛋白-1 核因子-κB 一氧化氮 一氧化氮合酶 叶酸
Abstract目的 探讨蛋氨酸负荷对去卵巢大鼠主动脉病变的影响及雌激素、叶酸、N-乙酰半胱氨酸的干预作用及其机制,为防治动脉粥样硬化提供新思路。 方法 将48只健康4月龄雌性SD大鼠随机分为6组,每组八只:(1) 假手术组(SHAM组)、(2) 去卵巢组(OVX组)、(3) 蛋氨酸组(去卵巢+蛋氨酸1 g. kg-1. d-1,MET组)、(4) 雌激素治疗组(去卵巢+蛋氨酸+17β-雌二醇0.1 mg.kg -1.d -1,ERT组)、(5) 叶酸治疗组(去卵巢+蛋氨酸+叶酸20 mg. kg-1. d-1,FA组)、(6) N-乙酰半胱氨酸治疗组(去卵巢+蛋氨酸+ N-乙酰半胱氨酸100 mg. kg-1. d-1,NAC组)。除SHAM组,其余各组大鼠行双侧卵巢切除术,SHAM组和OVX组灌服蒸馏水,其余各组给予蛋氨酸灌胃,术后一周开始药物干预。用药九周后,处死所有大鼠,测定血清总同型半胱氨酸(tHcy)、总胆固醇(TC)、甘油三酯 (TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和总抗氧化能力(TAC)、谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛 (MDA)、一氧化氮(NO)浓度;取主动脉制备HE病理切片,光镜观察主动脉形态学改变;免疫组织化学法观察主动脉组织核因子-κB(NF-κB)、单核细胞趋化蛋白-1(MCP-1)和内皮型一氧化氮合成酶 (eNOS)、诱导型一氧化氮合成酶(iNOS)的表达。 结果 1. 与SHAM组相比,OVX、MET组大鼠血清tHcy浓度明显升高(p < 0.01);与OVX组比,MET组大鼠血清tHcy浓度进一步升高(p < 0.01);与MET组相比,ERT、FA、NAC组大鼠血清tHcy浓度均明显降低(p < 0.01),但仍高于SHAM组水平。2. 与SHAM组相比,OVX、MET组血清TC、LDL-C浓度明显升高(p < 0.01), HDL-C浓度降低 (p < 0.05, p < 0.01);与OVX组比,MET组血清HDL-C浓度进一步降低 (p < 0.05);与MET组相比,ERT、FA、NAC 组血清TC、 LDL-C浓度均明显降低(p < 0.01),HDL-C浓度均明显升高(p < 0.01),接近SHAM组水平(p > 0.05);各组TG均无明显差异(p > 0.05);大鼠血清tHcy浓度与血清TC、LDL-C呈正相关(r = 0.295, p = 0.023; r = 0.367, p = 0.006)。3. 与SHAM组相比,OVX、MET组血清TAC、GSH-Px活性明显降低 (p < 0.01),MDA浓度明显升高 (p < 0.01);与OVX组相比,MET组血清中TAC、GSH-Px活性进一步下降 (p < 0.05, p < 0.01),而MDA浓度进一步明显升高 (p < 0.01);与MET组相比,ERT、FA、NAC 组血清TAC、GSH-Px活性明显升高,而MDA浓度明显下降 (p < 0.01),且FA、NAC组血清MDA浓度及NAC组GSH-Px活性均接近SHAM组水平(p > 0.05);大鼠血清tHcy浓度与血清TAC、GSH-Px呈显著负相关(r = -0.615, p = 0.000; r = -0.526, p = 0.000),与MDA 呈显著正相关(r = 0.724, p = 0.000)。4. 与SHAM组相比,OVX、MET组血清NO浓度明显降低(p < 0.01);与OVX组相比,MET组血清NO浓度进一步降低(p < 0.05);与MET组相比,ERT、FA、NAC组血清NO浓度均明显升高(p < 0.01),且ERT、NAC组血清NO浓度接近SHAM组水平(p > 0.05);大鼠血清tHcy浓度与血清NO呈负相关(r = -0.424, p = 0.002)。5. 与SHAM组相比,OVX、MET组大鼠主动脉出现泡沫细胞;与OVX组相比,MET组病变...
Other AbstractObjective To investigate the influence of methionine overload on artery lesions in ovariectomized rats and the intervene effect of estrogen 、folic acid and NAC to explore new idea for the prevention and treatment of atherosclerosis. Methods Healthy four-month-old female Sprague-Dawley rats (48) were randomly divided into six groups consisting of eight rats in each group:sham-operated group (SHAM group), ovariectomized group (OVX group), Ovx + methionine overload group (MET group, methionine 1g.kg-1.d-1), Ovx + Met +17β-estradiol replacement therapy group (ERT group, 17β-estradiol 0.1mg.kg-1.d-1), Ovx + Met + folic acid therapy group (FA group, folic acid 20mg.kg-1.d-1), Ovx + Met + N-acetylcysteine therapy group (NAC group, N-acetylcysteine 100mg.kg-1.d-1). The other groups were operated by bilateral ovariectomy except SHAM group. SHAM and OVX groups were administered with distilled water, and other groups with methionine overload. On 7th day after operation, drug intervention started and lasted for 9 weeks. All rats were sacrificed at the end of 9th week after operation. The levels of total homocysteine (tHcy), total cholesterol (TC), trigkyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), totle antioxidative capacity (TAC), malondialdehyde (MDA), nitric oxide (NO) in serum were measured respectively. HE slice of pathology were made of the aorta to observe the aorta histological changes by light microcopy. The expresssion of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), endothelial NOS (eNOS) and inducible NOS (iNOS) were detected by immunohistochemical method in aorta. Results 1. Compared with SHAM group, tHcy concentrations were increased significantly in OVX、MET groups ( p < 0.01); compared with OVX group, the tHcy were increased significantly in MET group ( p < 0.01); compared with MET group, the tHcy were decreased significantly in ERT、FA、NAC groups ( p < 0.01), they were higher than SHAM group. 2. Compared with SHAM group, TC、LDL-C were increased significantly ( p < 0.01) and HDL-C decreased ( p < 0.05, p < 0.01) in OVX、MET groups; compared with OVX group, HDL-C were decreased in MET group ( p < 0.05); compared with MET group, the TC、LDL-C were decreased and HDL-C increased significantly in ERT、FA、NAC groups ( p < 0.01), they had no difference with SHAM group; with TG, there was no significant difference in every gr...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223659
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
田盼丽. 蛋氨酸负荷对去卵巢大鼠主动脉病变的影响及叶酸、NAC的干预作用[D]. 兰州. 兰州大学,2009.
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