Mechanism of H2S-mediated ROCK inhibition of total flavones of Rhododendra against myocardial ischemia injury

Our previous studies have indicated that pretreatment with total flavones of Rhododendra flower (TFR) may protect against myocardial ischemic injuries in rats and mice. The cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathway have been associated with several cardiovascular diseases, but the effect of TFR on the Rho-associated protein kinase (ROCK) and CSE/H2S signaling pathways remains unknown. In the present study, the protective effects of TFR as a ROCK inhibitor in a mice model of myocardial infarction induced by isoproterenol (ISO) were investigated, and the hearts from the wild type and CSE knockout (KO) mice were examined. It was identified that the CSE KO mice exhibited decreased levels of ST segment elevation following anoxia/reoxygenation damage, increased LDH and CK-MB levels, aggravated pathological damage, and increased ROCK1, ROCK2 and MLC1 protein levels. In the CSE KO mice, there were no marked changes of the above experimental results between the TFR group and the model group. These results suggested that TFR-based inhibition of the RhoA/ROCK signal pathway may be mediated by the CSE-H2S signalling pathway and may be a novel therapeutic target for myocardial ischemia injury.