Inhibition of TNF-α by cyclophosphamide reduces myocardial injury after ischemia-reperfusion.

Purpose: The purpose of this study was to determine whether cyclophosphamide (CP) can decrease myocardial and systemic TNF-alpha 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-alpha was measured by cytometric bead array (CBA) and immunohistochemistry was used to detect TNF-alpha in myocardium. Results: Compared with I/R group, rats treated with CP showed a significant difference with decreased plasma TNF-alpha (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-alpha staining was down regulated. Conclusions: TNF-alpha is expressed in the myocardium and plasma after myocardial I/R injury. CP might be a feasible strategy for anti-TNF-alpha to protect myocardial FR injury.