Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage

Chuan Chih Hsu, Sheng Hsien Chen, Cheng Hsien Lin, Ming Chi Yung

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 μg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage) in mice.

原文英語
頁(從 - 到)1484-1496
頁數13
期刊Apoptosis
19
發行號10
DOIs
出版狀態已發佈 - 九月 18 2014

指紋

Hot Temperature
Apoptosis
Hypothalamus
Cells
Corticosterone
Adrenocorticotropic Hormone
Blood
Body Weight
Uridine Triphosphate
Heat Stroke
DNA Nucleotidylexotransferase
Cell adhesion
Endothelial cells
Metabolites
Platelets
Pyruvic Acid
Interleukin-1
Caspase 3
Hydroxyl Radical
Labeling

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Cancer Research
  • Pharmaceutical Science
  • Pharmacology
  • Medicine(all)

引用此文

Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage. / Hsu, Chuan Chih; Chen, Sheng Hsien; Lin, Cheng Hsien; Yung, Ming Chi.

於: Apoptosis, 卷 19, 編號 10, 18.09.2014, p. 1484-1496.

研究成果: 雜誌貢獻文章

Hsu, Chuan Chih ; Chen, Sheng Hsien ; Lin, Cheng Hsien ; Yung, Ming Chi. / Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage. 於: Apoptosis. 2014 ; 卷 19, 編號 10. 頁 1484-1496.
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