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

Ann Thorac Cardiovasc Surg. 2013;19(1):24-9. doi: 10.5761/atcs.oa.11.01877. Epub 2012 Aug 20.

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-α was 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-α staining 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclophosphamide / pharmacology*
  • Disease Models, Animal
  • Down-Regulation
  • Flow Cytometry
  • Immunohistochemistry
  • Myocardial Infarction / blood
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / immunology*
  • Myocardium / pathology
  • Rats
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Tumor Necrosis Factor-alpha
  • Cyclophosphamide