Inhibition of TNF-α by Cyclophosphamide Reduces Myocardial Injury After Ischemia-Reperfusion

Abstract

Purpose: The purpose of this study was to determine whether cyclophosphamide (CP) can decrease myocardial and systemic TNF-α expression and thus protects myocardial I/R injury.
Methods: Open chest rats were subjected to 30 min of ischemia followed by 3h, 12h or 24h of reperfusion. Rats were divided into sham group, I/R group and CP group, and each group included 3 timepoint subgroups (3h, 12h and 24h). Plasma TNF-αwas measured by cytometric bead array (CBA) and immunohistochemistry was used to detect TNF-α in myocardium.
Results: Compared with I/R group, rats treated with CP showed a significant difference with decreased plasma TNF-α (13.31 ± 2.62 vs 14.13 ± 5.95 pg/mL at 3 h reperfusion, 10.1 ± 2.73 vs 12.54 ± 5.00 pg/mL at 12 h reperfusion, 10.38 ± 5.59 vs 13.00 ± 3.59 pg/mL at 24 h reperfusion, p <0.05 respectively). Immunostaining was less intense with CP injection at each reperfusion time. The score of the intensity of myocardial TNF-αstaining was down regulated.
Conclusions: TNF-α is expressed in the myocardium and plasma after myocardial I/R injury. CP might be a feasible strategy for anti-TNF-α to protect myocardial I/R injury.