鹅去氧胆酸调控Nrf2通路缓解热应激小鼠肝脏损伤的研究

Chenodeoxycholic acid attenuates heat stress-induced liver injury by regulation of Nrf2 signaling pathway in mice

为了研究鹅去氧胆酸(CDCA)对热应激小鼠肝脏抗氧化能力的影响,试验选择体重18～22 g C57BL/6清洁级小鼠40只,随机分为4组(空白对照组、热应激组、低剂量组、高剂量组),每组10只。空白对照组、热应激组按照每10 g体重0.1 mL灌胃0.5%羧甲基纤维素钠(CMC-Na)溶液,低剂量组、高剂量组每千克体重分别灌胃50,100 mg CDCA,每天1次。每天灌胃结束后将热应激组、低剂量组、高剂量组小鼠置于42℃恒温培养箱2 h(12:00—14:00),重复处理7 d,测定肝脏组织中超氧化物歧化酶(SOD)活性与谷胱甘肽(GSH)含量,并以Western-blot方法分析小鼠肝脏中核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)与醌氧化还原酶1(NQO1)蛋白表达情况。结果表明:100 mg/kg CDCA可显著增加热应激小鼠肝脏组织中SOD活性及GSH含量(P<0.05),并且可极显著增加热应激小鼠肝脏中Nrf2、HO-1与NQO1蛋白表达水平(P<0.01)。说明CDCA可缓解热应激小鼠肝脏氧化损伤,具有潜在的临床应用价值。

To investigate the protective effect of chenodeoxycholic acid(CDCA) on heat stress-induced liver injury mice, Forty C57 BL/6 mice were randomly divided into 4 groups, including control, heat stress, low dose CDCA and high dose CDCA groups. There were 10 mice in each group.Mice in control and heat stress groups were given 0.5% carboxymethylcellulose sodium(CMC-Na) 0.1 mL per 10 g body weight, mice in low dose and high dose group were given 50 mg and 100 mg per kilogrammg CDCA by intragastric administration for once a day. During the 7 days treatments, mice were placed in a constant temperature incubator with the temperature of 42 ℃ for 2 hours(12:00—14:00). Then the activity of Superoxide dismutase(SOD) and Glutathion(GSH) were measured by commercial kits, besides, the protein expressions of Nuclear factor E2-related factor 2(Nrf2), Heme oxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1) were determined by Western-blot. The results showed that the activity of SOD and GSH were both increased after 100 mg/kg CDCA treatment(P<0.05), and Nrf2, HO-1 and NQO1 protein expression were also increased significantly(P<0.01), which indicated that CDCA could ameliorate heat stress-induced liver injury and benefit to promote future clinical trial applications.