Objectives The effect of ligustrazine (2,3,5,6-tetramethylpyrazine, TMP) on myocardial ischaemia reperfusion (IR) and the role of nitric oxide (NO) was investigated in a rat IR model.

Methods The animal model was built by ligation of the left anterior descending artery of rats. Sprague-Dawley rats were randomly divided into sham, IR (35 min of regional ischaemia followed by 120 min of reperfusion), 3 TMP pretreated (TMP pretreated, 5, 10, 30 mg/kg intravenous injection, 5 min before ligation) and TMP+L-NAME group. Infarct size, light microscopic evaluation, myocardial superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, the level of interleukin-1β (IL-1β) as well as NO production were measured.

Results Pretreatment with middle and high dose of TMP markedly decreased infarct size ((38.7±4.5)%, (35.2±2.3)% vs IR(50.4±4.6)%, p<0.05, respectively), increased SOD activity (50.2±3.2 U/mg, 51.2±6.4 U/mg vs IR 35.6±4.3 U/mg, p<0.05, respectively). Middle and high dose of TMP pretreatment decreased MDA content (0.417±0.069 nmol/mg, 0.331±0.023 nmol/mg vs IR 0.693±0.053nmol/mg, p<0.05, respectively) the MPO activity (6.237±0.901 U/mg, 6.201±1.263 U/mg, vs IR 8.670±1.260 U/mg, p<0.05, respectively), and the level of IL-1β (0.140±0.021, 0.132±0.027 pg/mg, vs IR 0.235±0.026 pg/mg, p<0.05). TMP pretreatment also alleviated the neutrophil infiltration and increased the NO level (0.404±0.041 µmol/g in the TMP-M group, 0.453±0.067 µmol/g in the TMP-H group vs 0.295±0.032 µmol/g in the IR group, p<0.05). However, these effects could be significantly reversed by L-NAME which abolished the increase of NO production brought by TMP.

Conclusions In conclusion, ligustrazine attenuated myocardial IR injury by a dose-related manner. The cardioprotective effect of ligustrazine may relate to its effects of increasing the level of NO, decreasing the inflammatory and oxidative stress.