- 作者: Chia-Chih Lin, Nan-Kuang Hsieh, Huey Ling Liou and Hsing I Chen
- 作者服務機構: Department of Physical Education and Kinesiology, National Dong Hwa University, Hualien, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Phorbol myristate acetate (PMA) is a strong neutrophil activator
and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a
compound of B complex. It exerts protective effects on the ALI caused by
various challenges. The purpose was to evaluate the protective effects of
niacinamide (NAC) on the PMA-induced ALI and associated changes.
Methods: The rat’s lungs were isolated in situ and perfused with constant flow.
A total of 60 isolated lungs were randomized into 6 groups to received Vehicle
(DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200
and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We
measured the lung weight and parameters related to ALI. The pulmonary
arterial pressure and capillary filtration coefficient (Kfc) were determined in
isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine
diphophate-ribose) polymerase] contents in lung tissues were detected.
Real-time PCR was employed to display the expression of inducible and
endothelial NO synthases (iNOS and eNOS). The neutrophil-derived
mediators in lung perfusate were determined.
Results: PMA caused increases in lung weight parameters. This agent
produced pulmonary hypertension and increased microvascular permeability.
It resulted in decrease in ATP and increase in PARP. The expression of iNOS
and eNOS was upregulated following PMA. PMA increased the
neutrophil-derived mediators. Pathological examination revealed lung edema
and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain
disclosed the presence of iNOS-positive cells in macrophages and endothelial
cells. These pathophysiological and biochemical changes were diminished by
NAC treatment. The NAC effects were dose-dependent.
Conclusions: Our results suggest that neutrophil activation and release of
neutrophil-derived mediators by PMA cause ALI and associated changes. NO
production through the iNOS-producing cells plays a detrimental role in the
PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative
effect on the PMA-induced ALI. NAC exerts protective effects on the
inflammatory cascade leading to pulmonary injury. This B complex compound
may be applied for clinical usage and therapeutic regimen.
- 中文關鍵字: --
- 英文關鍵字: phorbol myristate; niacinamide; acute lung injury; isolated perfused lungs; neutrophil-derived mediators; nitric oxide