RESUMEN
Ligustrazine, a compound extracted from roots of Ligusticum chuanxiong, is widely used in Chinese traditional medicine to treat cardiac and cerebrovascular diseases and pain, including angina. The mechanism(s) of ligustrazine's effect to reduce angina is not clear. Angina is mediated by cardiac afferent sensory neurons. These neurons display a large acid-evoked depolarizing sodium current that can initiate action potentials in response to acidification that accompanies myocardial ischemia. Acid-sensing ion channels (ASICs) mediate this current. Here we tested the hypothesis that ligustrazine reduces ischemia-induced cardiac dysfunction and acid-evoked pain by an action to inhibit ASIC-mediated current. The effects of ligustrazine to attenuate ischemia-induced ST-segment depression, T wave changes, and myocardial infarct size in hearts of anesthetized rats were determined. Effects of ligustrazine on currents mediated by ASICs expressed in cultured Chinese hamster ovary cells, and effects of the drug on acid-induced nociceptive behavior and acid-induced currents in isolated dorsal root ganglions cells were measured. Ligustrazine significantly attenuated acid-induced ASIC currents, reduced cardiac ischemia-induced electrical dysfunction and infarct size, and decreased the nociceptive response to injection of acid into the paw of the rat hindlimb. The ASIC channel inhibitor A-317567 similarly reduced electrical dysfunction, infarct size, and nociceptive behavior in the rat. Inhibition of ASICs by ligustrazine may explain at least in part the beneficial effects of the drug that are observed in patients with ischemic heart disease and angina.
RESUMEN
OBJECTIVE: To investigate the relationship between osteoprotegerin (OPG) system and acute coronary syndrome (ACS) and its classification according to traditional Chinese medicine (TCM). METHODS: A prospective study was conducted. The patients with ACS (n=210) and the patients with stable angina pectoris (SAP, n=200) were enrolled. The serum OPG and its ligand (sRANKL) were determined by enzyme-linked immunosorbent assay (ELISA), the OPG/sRANKL ratio was calculated, and the number of coronary vessels was involved, finally their relationship with the typing according to TCM was evaluated. One hundred and fifty non-coronary heart disease patients were enrolled as control. RESULTS: The serum OPG, OPG/sRANKL in ACS and SAP groups were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). The OPG, OPG/sRANKL in ACS groups were significantly higher than those in SAP group (both P<0.01). Serum OPG, OPG/sRANKL in ACS patients with different number of coronary vessel disease were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). OPG and OPG/sRANKL were gradually increased with increase in number of diseased coronary vessels, but the sRANKL descended (P<0.05 or P<0.01). Serum OPG and OPG/sRANKL were descended according to dialectical classification of TCM: Yang Qi weakening syndrome>Qi and blood stagnation syndrome>Qi deficiency with blood stasis syndrome>stagnation of phlegm blocks the heart-vessels syndrome>Yin deficiencies of the heart and the kidney syndrome>deficiency of both Qi and Yin syndrome, among them they were significantly higher in Yang Qi failure syndrome and Qi and blood stagnation syndromes than those of both Qi and Yin syndrome [OPG(ng/L): 621.38±32.86, 617.63±39.60 vs. 593.86±36.19, OPG/sRANKL(g/mol): 1 018.98±106.03, 1 011.27±121.61 vs. 942.16±115.82, P<0.05 or P<0.01]. Among different types of TCM in ACS group the serum sRANKL was significantly lower than that in control group (all P<0.01), but the difference among different types was not significant. CONCLUSIONS: Serum OPG, sRANKL, OPG/sRANK levels were related with incidence and severity of coronary lesions in ACS patients. Serum OPG and OPG/sRANKL ratio may have correlation with Yang Qi weakening syndrome and Qi deficiency with blood stasis syndrome.