Research Paper Volume 13, Issue 2 pp 3031—3044
Triptolide improves neurobehavioral functions, inflammation, and oxidative stress in rats under deep hypothermic circulatory arrest
- 1 Department of Cardiac Surgery, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, P. R. China
Received: October 23, 2020 Accepted: December 10, 2020 Published: January 19, 2021https://doi.org/10.18632/aging.202460
How to Cite
Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study investigated the neuroprotective effects of triptolide (TPL) in a rat model of cardiopulmonary bypass with deep hypothermia circulatory arrest (DHCA). Rats were randomly divided into six groups: control, sham, DHCA, and DHCA + TPL (100, 200, 300 μg/kg). Neurobehavioral functions were measured using the elevated plus-maze, Y-maze, and Morris water maze tests. Levels of inflammatory cytokines, oxidative stress indices, and brain neurotrophins were measured by ELISA. Microglial activation and cell death was measured by immunofluorescence staining and TUNEL assay, respectively. Finally, activation of the Nrf2 pathway and NF-κB were detected by western blot. The elevated plus-maze, Y-maze, and Morris water maze tests all showed that TPL mitigated anxiety-like behavior, working memory, spatial learning, and memory in DHCA rats. TPL inhibited inflammatory responses and oxidative stress, as well as increased brain neurotrophin levels in DHCA rats. Moreover, TPL attenuated microglia activation and cell death in DHCA rats. Finally, TPL activated the Nrf2 pathway and inhibited NF-κB activity in DHCA rats. These results demonstrated that TPL improved neurobehavioral functions, neuroinflammation, and oxidative stress in DHCA rats, which may be associated with the Nrf2 and NF-κB pathways.
DHCA: Deep hypothermia circulatory arrest; CPB: cardiopulmonary bypass; TPL: Triptolide; iv: Intravenous; Nrf2: Nuclear factor E2–related factor 2; ARE: Antioxidant response element; HO-1: Haemoxygenase-1; 8-OH-dG: 8-Hydroxydeoxyguanosine; DMSO: Dimethyl sulfoxide; MAP: Mean arterial pressure; BDNF: Brain-derived neurotrophic factor; NGF: Nerve growth factor; NT-3: Neurotrophin-3; NT-4: Neurotrophin-4.