袁嫣, 易娟, 赵婷婷, 郑济芳. Nrf2通路损伤介导铀诱导的大鼠急性肾毒性[J]. 环境与职业医学, 2016, 33(9): 869-873. DOI: 10.13213/j.cnki.jeom.2016.16286
引用本文: 袁嫣, 易娟, 赵婷婷, 郑济芳. Nrf2通路损伤介导铀诱导的大鼠急性肾毒性[J]. 环境与职业医学, 2016, 33(9): 869-873. DOI: 10.13213/j.cnki.jeom.2016.16286
YUAN Yan, YI Juan, ZHAO Ting-ting, ZHENG Ji-fang. Inhibiting of Nrf2 Pathway is Involved in Uranium-Induced Rat Acute Nephrotoxicity[J]. Journal of Environmental and Occupational Medicine, 2016, 33(9): 869-873. DOI: 10.13213/j.cnki.jeom.2016.16286
Citation: YUAN Yan, YI Juan, ZHAO Ting-ting, ZHENG Ji-fang. Inhibiting of Nrf2 Pathway is Involved in Uranium-Induced Rat Acute Nephrotoxicity[J]. Journal of Environmental and Occupational Medicine, 2016, 33(9): 869-873. DOI: 10.13213/j.cnki.jeom.2016.16286

Nrf2通路损伤介导铀诱导的大鼠急性肾毒性

Inhibiting of Nrf2 Pathway is Involved in Uranium-Induced Rat Acute Nephrotoxicity

  • 摘要: 目的

    研究Nrf2通路损伤与铀诱导的大鼠急性肾毒性的相关性及其机制。

    方 法

    成年雄性SD大鼠随机分成4组,每组6只,采用三种剂量的乙酸双氧铀(即2.5、5、10 mg/kg)单次腹腔注射大鼠,对照组注射生理盐水,收集24 h尿液。2天后,解剖肾脏,检测与分析反映肾功能的生化参数及氧化应激指标;HE染色观察肾组织病理形态变化;采用Western blot检测肾组织细胞中核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、谷氨酸-半胱氨酸连接酶催化亚基(GCLC)等基因的蛋白表达。

    结果

    急性铀中毒引起大鼠尿液中尿素氮与肌酐含量下降,而血清尿素氮和肌酐含量升高,损伤肾组织结构;铀染毒导致肾组织中丙二醛含量上升、还原性谷胱甘肽水平降低,抑制超氧化物歧化酶和过氧化氢酶的活性;低剂量铀染毒使胞核Nrf2含量升高,胞质Nrf2含量减少,增加Nrf2蛋白的核移位。而中、高剂量铀染毒降低Nrf2蛋白表达与核移位,也下调Nrf2通路下游的靶基因HO-1和GCLC的蛋白表达。

    结论

    急性铀染毒诱导了大鼠肾组织的氧化应激损伤,导致急性肾毒性,Nrf2通路损伤可能介导了铀诱导的大鼠急性肾毒性。

     

    Abstract: Objective

    To assess the relationship between Nrf2 pathway injury and uranium-induced acute nephrotoxicity in rats and related potential mechanism.

    Method

    Adult male SD rats were randomly divided into four groups with six rats each and intraperitoneally injected with a single dose of uranyl acetate at 2.5, 5, or 10 mg/kg or physiological saline (control group). The 24 h urine samples were collected. After two days, dissected kidneys were tested for kidney function related biochemical parameters and oxidative stress indicators. Pathological changes in kidney samples were observed after HE staining. The protein expressions of nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) in kidney tissue samples were detected by Western blot.

    Result

    The uranium exposure induced acute nephrotoxicity in rats with decreasing levels of urea nitrogen and creatinine in urine and increasing levels of urea nitrogen and creatinine in serum, indicating damaged renal tissue structure. The uranium exposure also induced an increasing level of malondialdehyde and a decreasing level of reduced glutathione, and suppressed activities of superoxide dismutase and catalase. The low-dose uranium exposure increased the nuclear Nrf2 level and decreased the cytosolic Nrf2 level. However, in the rats exposed to middle or high dose of uranium, a significant decrease was observed in the Nrf2 protein expression and nuclear translocation, as well as the protein expression of Nrf2-targeting HO-1 and GCLC genes.

    Conclusion

    Uranium exposure in rats induces oxidative stress injury which may cause acute nephrotoxicity. Nrf2 pathway damage could be involved in uranium-induced acute nephrotoxicity in rats.

     

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