Inhibition of NF-kappa B activation can attenuate ischemia/reperfusion-induced contractility impairment via decreasing cardiomyocytic proinflammatory gene up-regulation and matrix metalloproteinase expression.
Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, proinflammatory genes are up-regulated, and nuclear factor (NF)-kappaB is involved in this regulation. We studied whether inactivation of NF-kappaB could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB, attenuate matrix metalloproteinase (MMP) activation, and prevent cardiac mechanical dysfunction. Rabbits received normal saline (group 1) or curcumin (70 and 7 micromol/kg in groups 2 and 3) injection 2 hours before CPB. Total CPB was initiated, and myocardial protection was delivered every 20 minutes for 60 minutes of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 hours before the hearts were harvested. Blood was sampled at various time points. Postoperative expression of myocardial mRNA levels of interleukin 6, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, postreperfusion plasma level of troponin I, and cardiac mechanical dysfunction were significantly decreased in the curcumin groups. The myocardial levels of activated MMP-2 and -9 were also significantly reduced compared with the control group. In conclusion, by inhibiting NF-kappaB activation, the up-regulation of cardiac proinflammatory genes can be ameliorated, and the activation of MMPs can be decreased during CPB, thereby lessening severity of cardiac mechanical dysfunction after global cardiac ischemia/reperfusion injury.
Yeh
Chi-Hsiao
CH
Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan. yehccl@cgmh.org.tw
Lin
Yu-Min
YM
Wu
Yi-Cheng
YC
Lin
Pyng Jing
PJ
D000818:Animals; D003474:Curcumin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016328:NF-kappa B; D020782:Matrix Metalloproteinases; D003474:Curcumin