Liu P, Zhou Y S, Qin Y L, Li L, Liu Y, Xu B, Huang K, Ji C C, Lin F, Wang Y G, Li K, Chen S H, Shao L F, Mu J S
Department of Emergency, Intensive Care Medicine Center, 302 Hospital of PLA, Beijing 100039, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017 Nov 20;35(11):818-822. doi: 10.3760/cma.j.issn.1001-9391.2017.11.004.
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. Four experimental groups were designed.
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. 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. OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.
本研究旨在评估低聚原花青素(OPC)对百草枯(PQ)染毒小鼠的保护作用,并探讨其分子机制。设计了四个实验组。
10只BALB/c小鼠腹腔注射生理盐水。PQ组:10只BALB/c小鼠腹腔注射PQ(100mg/kg)。PQ+OPC组:10只BALB/c小鼠在暴露于PQ(100mg/kg)前1小时给予OPC(100mg/kg)。OPC组:10只BALB/c小鼠腹腔注射OPC(100mg/kg)。在设计的时间点采集外周血样本或肺组织样本,以检测氧化应激指标水平、核因子κB(NF-κB)通路和核因子红细胞相关因子2(Nrf2)通路的相关蛋白水平。与对照组相比,PQ组外周血中活性氧(ROS)水平、丙二醛(MDA)含量显著升高,超氧化物歧化酶(SOD)活性降低。与PQ组相比,PQ+OPC组外周血中ROS水平和MDA含量显著降低,SOD活性升高;PQ+OPC组肺组织中ROS水平和MDA含量也降低。此外,与对照组相比,PQ组肺组织中IκBα磷酸化和NF-κB p65表达增加。与PQ组相比,PQ+OPC组肺组织中IκBα磷酸化和NF-κB p65表达降低。另外,与对照组相比,OPC组肺组织中HO-1和Nrf2表达增加,而PQ组肺组织中这些表达降低。此外,与PQ组相比,PQ+OPC组肺组织中HO-1和Nrf2表达也增加。OPC可通过NF-κB和Nrf2通路调节氧化应激,减轻PQ诱导的小鼠全身毒性。