Objective: To observe the temporal expression of tumor necrosis factor-alpha (TNF-alpha) in myocardium and dorsal root ganglion (DRG) following ligation of the left anterior descending branch of coronary artery in the rats, and to explore the potential role of TNF-alpha in the neurogenic mechanisms induced by myocardial ischemia injury and the potential neurogenic mechanisms of acute local myocardial ischemia provoking global injuries of the heart.
Methods: Healthy adult male Sprague-Dawley rats weighing (275+/-15) g were randomly divided into three groups: Control group (n = 6), the samples were harvested from normal healthy rats directly after anaesthesia; Sham surgery group (group Sham, n = 24), with the same scheme of surgery except the procedure of coronary artery occlusion (CAO); CAO group (group CAO, n = 24), with ligation of the left anterior descending branch of coronary artery. Then group Sham and group CAO were further divided into four subgroups (each n = 6): group CAO 0.5 hour, group CAO 1 hour, CAO 3 hours, CAO 6 hours, after CAO for 0.5, 1, 3 and 6 hours respectively. Then rats were sacrificed as scheduled, and the samples were collected for immunohistochemistry (IHC), enzyme linked immunosorbent assay (ELISA) and real time reverse transcription-polymerase chain reaction (RT-PCR) tests to determine the changes in TNF-alpha and its mRNA in myocardium and DRG.
Results: (1)The expression of TNF-alpha and TNF-alpha mRNA in ischemic myocardium and non-ischemic myocardium increased significantly after CAO as compared with the baseline in the control group and that of Sham group ( P<0.05 or P<0.01), and they peaked at CAO 1 hour, but there was no significant difference in the level of expression between CAO 1 hour and CAO 0.5 hour groups (all P>0.05). The level of expression of TNF-alpha and TNF-alpha mRNA in ischemic myocardium were significantly higher than those in non-ischemic myocardium after CAO (all P<0.05). (2) The expression of TNF-alpha and TNF-alpha mRNA in DRG increased significantly after CAO as compared with the baseline in the control group and that of sham surgery control group, and they peaked at CAO 0.5 hour (P<0.05 or P<0.01).
Conclusion: CAO can provoke a significant increase in TNF-alpha and TNF-alpha mRNA in the myocardium (ischemic and non-ischemic) and DRG of rats. It demonstrates that acute myocardial ischemia, as a nociceptive stimulus, may activate the neurogenic reactions in body, and TNF-alpha might play an important role in the whole process, while the neurogenic mechanisms may contribute to the development of myocardial injury.
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