铁过载心、肾损伤及黄芩的干预作用
摘要
铁是生命体内必须的微量元素,是许多蛋白质和酶的重要组成部分。然而随着生活水平的提高,肉类在日常生活膳食中的比重逐渐增加,体内铁过载(Iron overload)的现象越来越普遍。目前,已有许多文献报道了铁催化产生活性氧自由基,引起周围组织的氧化应激增加是铁过载造成危害性主要的主要来源。而肝脏、心脏以及肾脏是铁超载受损的主要靶器官。黄芩苷作为一种天然的抗氧化剂,已有许多研究表明其具有抗氧化、抗炎、抗菌及抗肿瘤等生物活性。本文着重研究了黄芩苷对铁过载引起的心脏和肾脏损伤的干预作用。实验结果表明,铁过载破坏体内抗氧化系统,并引起组织氧化损伤及硝化损伤,黄芩苷的加入能减缓铁过载造成的肾组织氧化损伤,而在心脏中能起到部分保护作用。本文主要研究内容如下:
采用腹腔注射铁右旋糖酐(总铁量分别为150,300,500 mg Fe/kg bw)的方法造成大鼠慢性铁过载模型;与此同时,对总铁剂量为500 mg Fe/kg的大鼠喂以含1%黄芩苷的饲料。利用紫外可见分光光度法测定相关基本生化指标、原子吸收法测定组织总铁含量、免疫沉淀分析组织中蛋白质氧化和硝化等,来研究铁过载导致心、肾损伤的情况及黄芩苷的干预作用。结果显示:铁过载可以导致心脏和肾脏中总铁含量、脂质过氧化产物—丙二醛(MDA)含量、3-硝基酪氨酸含量及蛋白质氧化增加,并且肾脏中损伤程度与摄入铁剂量呈剂量依赖性,巯基含量、GPx活性、CAT活性及总抗氧化能力降低,但心脏中SOD活力增加。补充黄芩苷后没有显著降低两个组织中的总铁含量,但减少了肾脏中的氧化损伤,而在心脏中作用不明显,并且对不同抗氧化物酶活性的影响也不同,能明显增加总抗氧化能力和心脏中GPx活力,降低心脏SOD活力。
Iron is an essential trace element in organism. With the improving of living standards, the proportion of the meat in daily meal is increasing and the iron overload in our body happen more and more frequently. Iron overload was defined that a series of pathological changes in the body which induced by genetic factors or pathological conditions. In recent years, many studies have reported that the deleteriousness of iron overload caused organ damage through the generation of reactive oxygen species. Liver, heart and kidney are the main target organ to be injured in case of iron overload. Baicalin is an active antioxidant flavonoid, which have been researched in antioxidative and pharmacological effects for many years. In this thesis, the effect of baicalin on the iron-overload induced nephrotoxicity and cardiotoxic, have been studied in rats. The result indicated iron-overload reduces antioxidant status and enhance oxidative and nitrative damage. Supplementation of baicalin ameliorated iron-induced heart and kidney toxicity but is not completely protective. The main results are as follows:
The male rats were prepared by peritoneal injection of iron-dextran five times in two weeks to induce chronic iron overload, and the another positive control group was supplemented with baicalin containing diet (1% w/w) at the same time. Compared with control group, Fe content of iron-overload rats was clearly increased in heart and kidney, with concomitant increasing protein tyrosine nitration and oxidation stress like lipid peroxidation and protein oxidation. In iron-overload group, the activity of glutathione peroxidase, catalase, thiol group content and the total antioxidation status almost dose-dependently declined in both heart and kidney, except cardiac superoxide dismutase activity increased. Supplementation of baicalin increased glutathione peroxidase activity in both two tissues as well as attenuated oxidation injury in kidney.
采用腹腔注射铁右旋糖酐(总铁量分别为150,300,500 mg Fe/kg bw)的方法造成大鼠慢性铁过载模型;与此同时,对总铁剂量为500 mg Fe/kg的大鼠喂以含1%黄芩苷的饲料。利用紫外可见分光光度法测定相关基本生化指标、原子吸收法测定组织总铁含量、免疫沉淀分析组织中蛋白质氧化和硝化等,来研究铁过载导致心、肾损伤的情况及黄芩苷的干预作用。结果显示:铁过载可以导致心脏和肾脏中总铁含量、脂质过氧化产物—丙二醛(MDA)含量、3-硝基酪氨酸含量及蛋白质氧化增加,并且肾脏中损伤程度与摄入铁剂量呈剂量依赖性,巯基含量、GPx活性、CAT活性及总抗氧化能力降低,但心脏中SOD活力增加。补充黄芩苷后没有显著降低两个组织中的总铁含量,但减少了肾脏中的氧化损伤,而在心脏中作用不明显,并且对不同抗氧化物酶活性的影响也不同,能明显增加总抗氧化能力和心脏中GPx活力,降低心脏SOD活力。
Iron is an essential trace element in organism. With the improving of living standards, the proportion of the meat in daily meal is increasing and the iron overload in our body happen more and more frequently. Iron overload was defined that a series of pathological changes in the body which induced by genetic factors or pathological conditions. In recent years, many studies have reported that the deleteriousness of iron overload caused organ damage through the generation of reactive oxygen species. Liver, heart and kidney are the main target organ to be injured in case of iron overload. Baicalin is an active antioxidant flavonoid, which have been researched in antioxidative and pharmacological effects for many years. In this thesis, the effect of baicalin on the iron-overload induced nephrotoxicity and cardiotoxic, have been studied in rats. The result indicated iron-overload reduces antioxidant status and enhance oxidative and nitrative damage. Supplementation of baicalin ameliorated iron-induced heart and kidney toxicity but is not completely protective. The main results are as follows:
The male rats were prepared by peritoneal injection of iron-dextran five times in two weeks to induce chronic iron overload, and the another positive control group was supplemented with baicalin containing diet (1% w/w) at the same time. Compared with control group, Fe content of iron-overload rats was clearly increased in heart and kidney, with concomitant increasing protein tyrosine nitration and oxidation stress like lipid peroxidation and protein oxidation. In iron-overload group, the activity of glutathione peroxidase, catalase, thiol group content and the total antioxidation status almost dose-dependently declined in both heart and kidney, except cardiac superoxide dismutase activity increased. Supplementation of baicalin increased glutathione peroxidase activity in both two tissues as well as attenuated oxidation injury in kidney.
引文
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