Objective: The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism. Methods: Four experimental groups were designed.
Control group: 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure. OPC group: 10 BALB/c mice were intraperitoneally injected with OPC (100 mg/kg) . The peripheral blood samples or lung tissue samples were collected at the designed time points for measuring the levels of oxi-dative stress indicators, the related protein levels of nuclear factor-kappa B (NF-κB) pathway and nuclear fac-tor erythroid related factor-2 (Nrf2) pathway. Results: Compared with the control group, the level of reactive oxygen species (ROS) , the content of malondialdehyde (MDA) in the PQ group were significantly induced, and the activity of superoxide dismutase (SOD) in the PQ group was decreased in the peripheral blood. As com-pared with the PQ group, the level of ROS and the content of MDA in the PQ+OPC group were significantly re-duced, the activity SOD in the PQ+OPC group was increased in the peripheral blood; the level of ROS and the content of MDA were also reduced in lung tissues in the PQ+OPC group. Moreover, compared with the con-trol group, the phosphorylation of IκBα and the expression of NF-κB p65 were increased in lung tissues in the PQ group. The phosphorylation of IκBα and the expression of NF-κB p65 were decreased in lung tissues in the PQ+OPC group as compared with the PQ group. In addition, compared with the control group, the expressions of HO-1 and Nrf2 were increased in lung tissues in OPC group, and these were decreased in lung tissues in PQ groups. Furthermore, the expressions of HO-1 and Nrf2 were also increased in lung tissues in PQ+OPC as com-pared with the PQ group. Conclusion: OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.
目的： 探讨低聚原花青素（oligomeric proanthocyanidins，OPC）对百草枯（paraquat，PQ）中毒的预防保护作用，并探讨作用的分子机制。 方法： 将动物分为对照组（10只，腹腔注射生理盐水）、PQ染毒组（10只，经腹腔注射PQ 100 mg/kg），PQ和OPC联合染毒组（PQ+OPC组，10只，小鼠首先腹腔注射OPC 100 mg/kg，1 h后一次性注射PQ 100 mg/kg）和OPC组（10只，腹腔一次性注射OPC 100 mg/kg）。收集外周血及肺组织样本，检测OPC对PQ诱导的活性氧（ROS）水平、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活力的影响；Western blotting检测OPC对PQ诱导的NF-κB通路和核Nrf2通路关键蛋白表达的影响。 结果： 与对照组比较，PQ组外周血淋巴细胞中ROS水平和MDA含量明显升高，SOD活力明显下降，差异有统计学意义（P<0.05）。与PQ组比较，PQ+OPC组外周血淋巴细胞中ROS水平及MDA含量明显降低、SOD活力明显升高，差异有统计学意义（P<0.01）。与PQ组比较，PQ+OPC组肺组织ROS水平和MDA含量明显下降，差异有统计学意义（P<0.05）。与对照组比较，PQ组肺组织中IκBα磷酸化水平及NF-κB p65亚基的表达明显升高，差异有统计学意义（P<0.01）。与PQ组比较，PQ+OPC组肺组织中IκBα磷酸化及p65表达明显下降，差异有统计学意义（P<0.05）。与对照组比较，OPC组肺组织中HO-1及Nrf2蛋白的表达水平明显升高，PQ组中HO-1及Nrf2蛋白的表达水平明显降低，差异有统计学意义（P<0.01）；与PQ组比较，PQ+OPC组肺组织中HO-1及Nrf2蛋白的表达水平明显升高，差异有统计学意义（P<0.05）。 结论： OPC可以通过调节氧化应激，调控NF-κB和Nrf2通路信号，减轻PQ诱导的氧化损伤。.
Keywords: Acute lung injury; Oligomeric proanthocyanidins; Oxidative stress; Paraquat.