Study On Cardiovascular Pharmacological Effects Of Total Glycosides Of Ranunculus Japonicus

This thesis is composed of three parts. PartⅠmainly introduced inhibitory effect of total glycosides of Ranunculus japonicus(TGRJ) on proliferation of thoracic aortic vascular smooth muscle cells induced by norepinephrine. PartⅡcovered my study on the influence of TGRJ on multiple factors induced contraction of rats'thoracic aorta and my discussion related to possible mechanisms. PartⅢreported protective effect of TGRJ on myocardial ischemia in mice caused by pituitrin.PartⅠInhibitory effect of TGRJ to norepinephrine-induced proliferation of thoracic aortic vascular smooth muscle cellsIn this thesis, norepinephrine-induced thoracic aortic vascular smooth muscle cells cultured in vitro as cell proliferation model, phentolamine and nimodipine as positive control drugs, methyl thiazolyl tetrazolium colorimetric assay was applied to observe the inhibitory effect of TGRJ to norepinephrine-induced proliferation of thoracic aortic vascular smooth muscle cells. Result showed that TGRJ at and over concentration of 200μg/ml had significantly inhibitory effect on proliferation of thoracic aortic vascular smooth muscle cells in general cultivation (p<0.05) while 12.5μg/ml～100μg/ml TGRJ had no significant effect on it but had significantly inhibitory effect on proliferation induced by norepinephrine of thoracic aortic vascular smooth muscle cells (p<0.05) with dose and time dependent manner.PartⅡStudy on the influence of TGRJ to multiple factors induced contraction of rats'thoracic aorta and investigation of possible mechanisms In this thesis, isolated aortic ring tension recording method was applied to further observe the effects of TGRJ on multiple factors-induced vasoconstriction of isolated thoracic aortic ring, also investigation on its action sites and possible action mechanisms. Results showed that, TGRJ had markedly inhibitory effect on vasoconstriction induced by norepinephrine, potassium chloride or calcium chloride solution (p<0.05), and the effect of which was with dose dependent manner and without endothelium dependent manner. And the results concluded that its possible mechanisms have relation withα1 adrenoceptor antagonist and calcium channels block which lead to decrease intracellular calcium release and calcium influx so as to decrease calcium concentration in cytoplasm.PartⅢProtective effect of TGRJ to pituitrin caused myocardial ischemia on mice In this thesis, the electrocardiographs (ECGs) leadⅡwere monitored in myocardial ischemia rats caused by pituitrin through tail vein in order to observe the effect of TGRJ on myocardial ischemic in mice induced by pituitrin. Results showed that total glycosides of ranunculus japonicus have effect on reducing the rise amplitude of T-wave and inhibiting decent of heart rates to a certain degree compared with NS groups(p<0.05) in electrocardiogram. The effects of high dose groups were superior to low dose groups'. No significant difference of the effects was showed between intragastric administration and intraperitoneal administration. These results demonstrated that total glycosides of Ranunculus japonicus possesses protective effects on myocardial ischemia caused by pituitrin.