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氧化应激与克山病关系的现场流行病学及动物实验研究
中文摘要

 目的:克山病是一个严重危害病区人民身体健康的地方性公共卫生问题,研究人群硒蛋白P (Se-P)含量与克山病关系的相关研究未见报道。本课题主要研究含硒蛋白家族中功能可能更为重要的Se-P与克山病的关系,分析低硒、低蛋白所致的氧化应激在克山病发病过程中的作用。通过现场流行病学调查寻找克山病可能的发病危险因素,并通过动物实验予以验证。从现场调查和动物实验两个方面综合寻找病因线索,分析发病机制,为克山病的现阶段预防提供依据。 方法:1、现场流行病学研究:我们以按照克山病诊断标准确诊的克山病患者作为研究对象,分别在病区和非病区选取健康者作为对照人群,对所有人员进行流行病学问卷调查。同时采集土壤、粮食样品以及人群血样,实验室检测土壤硒、粮食硒含量;人群血硒含量、Se-P含量、GSH-PX活力、SOD活力、MDA含量。2、动物实验研究:根据现场研究所得到的结果,通过动物模型予以验证。将40只健康雄性Wistar大鼠按体重随机分为两组,即低硒低蛋白组和常硒常蛋白组,饲养六个月后处死,测定Se-P、GSH-PX、SOD、MDA、ROS水平,计算心脏质量指数,光镜、电镜观察大鼠心肌组织形态及超微结构的变化。运用SPSS13统计软件进行t检验、方差分析、SNK检验、χ²检验及Logistic回归分析处理数据。 结果:1、现场调查结果:年人均收入水平低可能是克山病发病的危险因素。经常食用动物性蛋白及大豆蛋白、新鲜蔬菜、水果以及果仁类等食品可能是克山病发病的保护性因素。病区的土硒、粮硒含量显著低于非病区;病例组全血硒含量、Se-P含量、GSH-PX活性、SOD活力与内外两个对照组比较显著降低,而MDA含量显著高于内外两个对照组。在衡量机体硒营养状态的三项指标中,血浆Se-P水平与克山病的关联最为密切;2、动物实验结果:低硒低蛋白组Se-P含量、GSH-PX活力、SOD活力低于对照组,而MDA含量、R0S活力高于对照组。低硒低蛋白组心脏质量指数明显高于对照组,心肌坏死率也高于对照组。低硒低蛋白组大鼠心肌出现明显的组织形态和超微结构的病理性改变。 结论:微量元素硒及膳食蛋白质等作养物质摄入的减少可能与克山病的发生有一定的关系。克山病病人机体内存在抗氧化硒蛋白含量减少所致的抗氧化能力降低,氧化损伤增强。Se-P在克山病的发病过程中可能具有保护作用,可以考虑将其作为克山病病人体内硒营养水平的评价指标。动物实验结果表明低硒低蛋白能够造成大鼠体内抗氧化硒蛋白含量的减少,使大鼠体内处于氧化与抗氧化失平衡状态;心肌组织形态和超微结构呈现病理性改变。 关键词:硒蛋白P;谷胱甘肽过氧化物酶;克山病;病例对照研究;氧化应激;心肌坏死

英文摘要

 Objective: Keshan disease (KD) is a serious endemic public health issue. The relationship between selenoprotein-P (Se-P) and KD had not been reported so we studied the relationship between selenoprotein-P and Keshan disease and explored the role of oxidative stress caused by selenium deficiency and low protein. We, first, conducted a case-control study on the risk factors of KD were in the KD areas in Heilongjiang province; then, the animal experiments based on the results of the case-control study. Methods: 1. The case-control study was to find the risk factors of KD. According to the diagnostic criteria of KD, cases were from KD affected areas of Heilongjiang province, controls were chosen at same KD affected areas (internal controls) and non KD affected areas (external controls). The levels of blood selenium, Se-P, maleic dialdehyde (MDA) and activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) of the KD cases, the internal controls and the external controls were measured. The levels of the main foods and soil of the same areas were also measured. 2. Animal experiments: 40 Wistar rats were randomly divided into 2 groups according to body weight, i.e. the low Se and protein group and normal Se and protein group. After 6 months feeding, all animals were killed, and levels of Se-P, GSH-PX, SOD. MDA, and ROS of these animals were analyzed, and heart mass index and myocardial pathology changes were observed with light microscope and electronic microscope. SPSS13 was used for the statistical analysis in this study. Results: 1. The case-control study: low living standard might be a risk factor of KD and regular intake of protein, fresh vegetable, fruit and nut might play a protection role. Compared with those in non-disease areas, the selenium levels of food and soil in disease area were significantly lower. Compared with two control groups, the levels of blood selenium, Se-P, GSH-PX and SOD of KD patients were significantly lower, and the levels of MDA were statistically higher. Serum Se-P level was significantly associated with KD. 2. Animal experiments: Compared with control group, the levels of Se-P, GSH-PX, and SOD were lower, and levels of MDA and ROS were higher in low Se and protein group, and heart mass index and incidence rate of injured myocardium also higher, we observed the obvious tissue form and ultrastructural pathological changes in this group. Conclusions: Low intake of trace element selenium and protein may be associated with KD. Oxidative stress caused by low selenoproteins was found in KD patients. The levels of Se-P should be considered as a marker of selenium exposure according to its potential protecting role. Low intake of selenium and protein could result in low selenoproteins, which lead to oxidative stress associated with myocardium damage. We observed obviously tissue form and ultrastructural pathological changes in this group. Key words: selenoprotein; glutathione peroxidase; Keshan Disease; case-control study; oxidative stress; myocardial damage

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