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Protective Effects On Myocardial Ischemia Injury Of TFA And Its Pharmacological Preconditioning Mechanism

Posted on:2004-06-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:L FanFull Text:PDF
GTID:1104360122998913Subject:Cardiovascular and cerebrovascular pharmacology
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Total flavone of Abelmoschl Manihot L medic (TFA) was extracted from the flower of Abelmoschus, which has been preliminary assessed to be of protection against myocardial ischemia given via intragastric administration (ig) route. It is known that the absorption of flavonoides is poor when given intragastricly. The low bioavailability would affect their validity. The advanced study on the protective effect of TFA against ischemic myocardium injury and its pharmacological pre-conditioning mechanisms through intravenous injection (iv) was performed in this paper:1 Prolongating effect of TFA on ECG survival time in trachea clamping miceOn the myocardial anoxia model induced by clamping trachea in mice, it is found that the ECG survival time were much longer in the groups pretreated with TFA (32,16, 8 mg kg-1) than that in NS control group. The maximal elongation rate of ECG survival time reached a height of 37.88%.2 Protective effect of TFA on the acute myocardial ischemia injury in mice induced by isoproterenolAcute myocardial ischemia episodes and typical ischemia ECG developed after subcutaneous injection (sc) of Iso continuously. The animals were pretreated with TFA at doses of 32, 16 or 8 mg kg-1 administrated intravenously at 10 minutes before giving Iso once a day for 3 days. On the third day, ECG was recorded at the end of sc Iso. 20minutes later, the mice were killed, the wet weights of myocardium were weighted immediately. Their dry weights were weighted after 8 hours baking at 110C. The results showed that the myocardial water content (MWC) and the myocardial index (MI)in model group were 1.96% and 27.04% higher than NS control. TFA (16mg kg-1) can significantly inhibit the increase of MWC of model group. Its inhibition rate was 65.82%. TFA (32, 16mg kg-1) can also remarkably inhibit the increase of MI of model group and the inhibition rates were 47.48% and 65.82% respectively. Moreover, TFA showed remarkedly the amelioration effect on the abnormal changes of ECG vs the model control.3 Protective effect of TFA on myocardial ischemia reperfusion injury (IRI) in rat Langendorff heartsUsing the isolated perfused rat heart as a model set up by Langendorff, it was found that TFA( 100,50, 25mg L-1) can obviously increase the activity of superoxide dismutase (SOD) in myocardium homogenates, significantly reduce the lipid peroxidation product, malondialdehyde (MDA) , decrease the transudation of creatine phosphokinase(CPK) and lactate dehydrogenase (LDH) from cardiomyocyte. And also, TFA remarkedly raised nitric oxide (NO) level and the activity of NO synthase( NOS).4 TFA increases the blood flow volume of left circumflex branch of coronary (LCX) in dogsIt was found that TFA (16mg kg-1) can significantly increase the LCX blood flow in dogs determined by the electromagnetic flow meter at lOminute after administration of TFA and the effect lasted foe over 15 minutes.5 Protective effect of TFA-PP on IRI in rabbitsBefore the 30 minutes ischemia and the followed 60 minutes reperfusion, the rabbit hearts were preconditioned with 5 minutes ischemia and 10 minutes reperfusion so as to elicit cardioprotection of ischemic preconditioning (IP). In order to mimic IP, before ischemia reperfusion (IR), different doses of TFA were perfused intra-venously for 5 minutes, then followed a 10 minutes break. The results showed that TFA (16, 8, 4mg kg-1) could ameliorate the abnormal changes of ECG (ST segment and T wave), decrease the incidence rate of cardiac arrhythmia. And also, TFA at the samedoses significantly reduce the content of lactic acid (LD) in myocardial homogenate, decrease the transudation of lactate dehydrogenase (LDH) from myocardial cells, enhance the activities of SOD and glutathione peroxidase (GSH-PX), decrease MDA level in plasma. Meanwhile, TFA could also reinforce the activity of NOS, increase the content of NO in plasma. Such effective changes of biochemical markers in TFA groups are about the same as IP group.6 Effect of TFA on the expression of the ap...
Keywords/Search Tags:TFA, myocardial ischemia, ischemia reperfusin injury, pharmacological preconditioning
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