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花青素对镉诱导肝脏损伤的保护作用及机制研究
Protective Effect and Mechanism of Anthocyanidin on the Cadmium-induced Hepatotoxicity in Rats

导  师: 马养民

学科专业: G03

授予学位: 硕士

作  者: ;

机构地区: 陕西科技大学

摘  要: 镉(CADMIUM,CD),是一种常见的环境污染物。由于其生物半衰期长,代谢缓慢,因此毒性极强;能够引起多种组织和器官的损伤,并诱发畸形导致基因突变。其中,以肝脏损伤的镉中毒备受关注。已有研究认为,镉的肝脏毒性与自由基的积累和氧化压力(OXIDATIVESTRESS,OS)的产生有关,因此寻找高效、安全的抗氧化物成为肝脏解毒的主要方向。鉴于花青素(ANTHOCYANIDIN)是一类具有超强自由基清除能力的天然抗氧化物,并且在蓝莓(BLUEBERRY)中储量丰富,故本文通过实验,研究蓝莓花青素(AY)对小鼠镉损伤肝脏的保护作用及其作用机制。 体外实验中,通过分光光度法讨论... Cadmium /(Cd/) is a common environmental pollutant and it hassevere biotoxicity due to the long half biological period and slowbiological metabolism. Cd that circulates with blood is capable ofcausing organ damages and inducing genetic mutation. Liver is reportedto be an easy target organ where Cd accumulates. The liver damageinduced by Cd is associated with its capability of overproduction of freeradicals and generation oxidative stress. Hence, antioxidants with highefficiency and safety may exert liver detoxification against Cd injuries.Anthocyanidins /(Ay/) is a kind of widespread natural plant pigments,showing a super radical scavenging capacity. For most species,blueberry is so far found to rich in Ay and serves as the priority sourcefor Ay. The present study aims to investigate the protective effect andmechanism of Ay extracted from blueberry on the cadmium-inducedhepatotoxicity in mice. In vitro experiments, the scavenge capability of Ay to hydroxylradical /(OH/) and DPPH are studied via spectrophotometry and thechelation ability of Cd2+against Ay are evaluated. In vivo experiments,we developed a model to evaluate the counter effect of Cd-induceddamage and the protective effect of Ay on mice by measuring the weightof body and liver as well as liver coefficient. Besides, the content of Cdand Zn in liver cells are examined by atomic absorptionspectrophotometer. The antioxidant levels as well as the degree of celloxidation in liver were examined correspondingly; H/&E dyeing andparaffin sections were also utilized for histopathological analysis. Toquantitatively analysis Cd genotoxicity, the damaged DNA was furthermeasured via the methods of agarose gel electrophoresis anddiphenylamine. The present results showed that Ay extracted from blueberries hasan excellent radical scavenging capacity dependent upon itsexperimental dose and the chelation between Cd and Ay which is inaccordance with the in vitro observation. The mice feed by Cd poorlygrow and their livers show obvious damage. It is observed that in themice fed by Ay and Cd, however, the accumulation of Cd in liver isinhibited and liver cell functions are restored, contributing to micegrowth. Moreover, Ay can significantly improve the vitality ofsuperoxide dismutase /(SOD/) and catalase /(CAT/), leading to thereduction of oxidative stress. The concentration of madondialdehyde/(MDA/), protein carbonyl /(PCO/) and nitric oxide /(NO/) in liver islowered and therefore the fragmentation of DNA and apoptosis aresuppressed. In addition, histopathology shows that Ay can prevent livercell shrinkage, nucleoplasm outflows and inflammatory infiltrationinduced by Cd. Ay shows a dose-dependent manner against theCd-induced liver damage in tests. In conclusion, the mechanisms of Ayto protect cadmium-induced hepatotoxicity in mice may involve in i/)the scavenging of free radicals and improvement of antioxidant abilities;ii/) inhibition of NO release and other inflammatory cytokines; iii/)chelation of Cd2+to reduce cadmium accumulation in liver cells.

关 键 词: 花青素 镉诱导 肝脏损伤 自由基 氧化应激

分 类 号: [Q946.836 Q504]

领  域: [生物学] [生物学]

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