College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, China.
Environ Pollut. 2018 Jun;237:377-387. doi: 10.1016/j.envpol.2018.02.035. Epub 2018 Mar 15.
Lead, a pervasive environmental hazard worldwide, causes a wide range of physiological and biochemical destruction, including metabolic dysfunction. Grape seed proanthocyanidin extract (GSPE) is a natural production with potential metabolic regulation in liver. This study was performed to investigate the protective role of GSPE against lead-induced metabolic dysfunction in liver and elucidate the potential molecular mechanism of this event. Wistar rats received GSPE (200 mg/kg) daily with or without lead acetate (PbA, 0.5 g/L) exposure for 56 d. According to biochemical and histopathologic analysis, GSPE attenuated lead-induced metabolic dysfunction, oxidative stress, and liver dysfunction. Liver gene expression profiling was assessed by RNA sequencing and validated by qRT-PCR. Expression of some genes in peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway was significantly suppressed in PbA group and revived in PbA + GSPE group, which was manifested by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated by western blot analysis. This study supports that dietary GSPE ameliorates lead-induced fatty acids metabolic disturbance in rat liver associated with PPARα signaling pathway, and suggests that dietary GSPE may be a protector against lead-induced metabolic dysfunction and liver injury, providing a novel therapy to protect liver against lead exposure.
铅是一种在全球范围内普遍存在的环境危害物，它会导致广泛的生理和生化破坏，包括代谢功能障碍。葡萄籽原花青素提取物（GSPE）是一种具有潜在代谢调节作用的天然产物，可在肝脏中发挥作用。本研究旨在探讨 GSPE 对铅诱导的肝脏代谢功能障碍的保护作用，并阐明这一事件的潜在分子机制。Wistar 大鼠连续 56 天每天接受 GSPE（200mg/kg）或同时接受 GSPE 和醋酸铅（PbA，0.5g/L）暴露。根据生化和组织病理学分析，GSPE 减轻了铅诱导的代谢功能障碍、氧化应激和肝功能障碍。通过 RNA 测序评估肝脏基因表达谱，并通过 qRT-PCR 进行验证。过氧化物酶体增殖物激活受体α（PPARα）信号通路中一些基因的表达在 PbA 组中显著受到抑制，而在 PbA+GSPE 组中得到恢复，这通过基因本体分析、京都基因与基因组百科全书通路分析得到证实，并通过 Western blot 分析进行了验证。本研究支持膳食 GSPE 可改善铅诱导的大鼠肝脏脂肪酸代谢紊乱，与 PPARα 信号通路有关，并表明膳食 GSPE 可能是预防铅诱导的代谢功能障碍和肝损伤的保护剂，为保护肝脏免受铅暴露提供了一种新的治疗方法。
