Nuclear factor-kappaB-regulated cyclooxygenase-2 expression in surgery-associated paraspinal muscle injury in rats.
OBJECTIVE
Paraspinal muscle injury is a common but neglected complication of posterior spinal surgery. Evidence suggests that surgical retraction places mechanical and oxidative stress on the paraspinal muscles and that inflammation is a major postoperative pathological finding in the muscles. The roles of cyclooxygenase (COX)-2 and nuclear factor (NF)-kappaB in the inflammatory processes after retraction remain to be clarified.


METHODS
In the control group, paraspinal muscles were dissected from the spine via a posterior incision and then laterally retracted. Paraspinal muscle specimens were harvested before as well as at designated time points during and after persistent retraction. The time course of NF-kappaB activation was determined by gel shift assay. Expression of COX-2 was examined using Western blot analysis and immunohistochemistry. The severity of inflammation was evaluated based on histopathology and myeloperoxidase (MPO) activity. The NF-kappaB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. Retraction induced early activation of NF-kappaB in paraspinal muscle cells. The expression of COX-2 could not be detected until 1 day postoperativley, reaching a peak at 3 days. The time course of COX-2 expression correlated with that of inflammatory responses and MPO activity. Pretreatment with PDTC inhibited intraoperative NF-kappaB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Postinflammation fibrosis was also abolished by PDTC administration.


CONCLUSIONS
Both NF-kappaB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. The therapeutic strategy of NF-kappaB inhibition may be applicable to the prevention of such injury.
Lu
Kang
K
Department of Neurosurgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University, Kaohsiung, Taiwan.
Liang
Cheng-Loong
CL
Chen
Han-Jung
HJ
Chen
Shang-Der
SD
Hsu
Huan-Chen
HC
Chen
Yun-Ching
YC
Hsu
Fu-Fei
FF
Cho
Chung-Lung
CL
D000818:Animals; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2; D004247:DNA / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000601:surgery*; D014947:Wounds and Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D007527:Isoenzymes; D016328:NF-kappa B; D003094:Collagen; D004247:DNA; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases