TFAM公司
线粒体生物发生
内分泌学
内科学
线粒体
肿瘤坏死因子α
生物
医学
细胞生物学
作者
Lonneke Smeding,Willem J. van der Laarse,T. A. van Veelen,Regis R. Lamberts,Hans W.M. Niessen,Martin C. J. Kneyber,A. B. Johan Groeneveld,Frans B. Plötz
标识
DOI:10.1016/j.jss.2011.05.055
摘要
Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis.Rats received lipopolysaccharide (LPS, n = 11) intraperitoneally. Healthy rats (n = 6) served as controls. Myocardial function was measured ex vivo in an isolated Langendorff-perfused heart set-up. Myocardial vascular cell adhesion molecule-1 (VCAM-1) expression was determined by immunofluorescence microscopy. Cytochrome c release and cytochrome c oxidase (COX IV) activity were measured by immunohistochemistry and enzyme histochemistry, respectively. Protein expression of tumor necrosis factor-α (TNF-α), B-cell lymphoma (Bcl)-2, peroxisome proliferator activated receptor γ cofactor 1α (PGC-1α), and mitochondrial transcription factor A (TFAM) were analyzed by Western blot technique. Mitochondria were studied by electron microscopy.Two hours after LPS injection, developed pressure had decreased and after 4 h myocardial contractility (+dP/dt) and relaxation (-dP/dt) also had decreased. TNF-α protein expression was increased after 2 h and returned to normal at 4 h, whereas after 4 h VCAM-1 expression was higher in LPS-treated animals. At 2 h a substrate-dependent increase in COXIV-activity was seen, but no mitochondrial damage occurred as cytochrome c release, COX IV activity and Bcl-2, PGC-1α or TFAM expression were not changed. Electron microscopy did not reveal differences in myocardial mitochondrial characteristics between LPS-treated and control rats.Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.
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