Research Of The Effects And Metabolism Of Arachidonic Acid And Cyclovirobuxine-D On Myocardial Ischemia

Section I Reaserch of the effects of arachidonic acid on myocardial ischemia and its mechanismObjective To investigate the interfering effects of arachidonic acid(AA) in the formation of myocardial ischemia and its mechanism.Methods (1). The model of hyperlipidemia was established with high cholesterol diet in rabbits. Coefficient of viscera were measured.The effects of arachidonic acid on Triglycerides(TG), total serum cholesterol (TC) , LDL were measured. Atherosclerotic plaquems were measured. The pathologic changes of aorta and liver were observed and the ratio of lesion to intimal area, intimal thickening and intima-to-media tatio were calculated. (2). The effect of arachidonic acid on Malondialdehyde(MDA) and SOD(both in serum and liver) were measured. The expressions of iNOS and ecNOS, bcl-2 and Bax in aorta and liver were investigated on the pathological sections by immunohistochemistry staining. (3). The model of human umbilical vein endothelial cells(HUVECs, ECV304) from injury induced by hyperlipidemic serum(HLS) was established.The cell viabilities were monitored by MTT assay. The contents of MDA, SOD and NO, ET-1 were measured. The expressions of iNOS and eNOS in aorta and liver were investigated on the pathological sections by immunohistochemistry staining.Result (1). Compared with the normal group, coefficient of liver of the model group increased obviously, and coefficient of thymus decreased obviously, TG, TC, LDL of the model group increased obviously.There was a lot of fatty tissue accumulating on the aorta of the model group, unflat aortic tunica intima, disordered SMC of tunica media, detached elasrtic coat, cellular swelling and lipid droplet could be seen under light microscope of the model group. TG, TC, LDL of the babbits of atherosclerosis could be decreased markedly by AA, the ratio of lesion to intimal area decreased by 54.43%(P<0.01), intimal thickening and intima-to-media tatio respectively reduced by54.30%(P<0.01) and 48.77% (P<0.01). (2). In model group, MDA content of serum increased obviously, and SOD lever in liver decreased obviously, the expression of eNOS and bcl-2 decreased, the expression of iNOS and Bax increased. MDA and SOD of the babbits of atherosclerosis could be decreased markedly by AA, the expression of eNOS and bcl-2 of the A A group increased, the expression of iNOS and Bax of the AA group decreased. (3). The cell viability and NO content of endothelial cells were decreased markedly by HLS, and the effects could be restrained to different extent by AA of the concentrations of 2mmol/I^ 4mmol/I^ 8mmol/L. MDA lever and ET-1 lever were increased markedly by HLS, and the effects also could be restrained to different extent by AA of the concentrations of 2mmol/L> 4mmol/l^ 8mmol/L. After the endothelial cells were incubated for 48h, there were light yellow iNOS distributing in the cells of control group, and deep brown iNOS in the cells of modell group, and deep brown iNOS in AA group of lmmol/L, when the concentrations of AA were increased to 2^ 4> 8mmol/L, the colour were changed from deep brown to yellow, and the ratio of positive cells decreased. After the endothelial cells were incubated for 24h, there were deep brown eNOS distributing in the cells of control group, and deep yellow eNOS in the cells of modell group, and deep yellow eNOS in AA group of lmmol/L, when the concentrations of AA were increased to 2^ 4> 8mmol/L, the colour were changed to light brown, and the ratio of positive cells increased.Conclusion In the formation of atherosclerosis, the function of lipid metabolism and antioxidation of liver may be important, so protecting liver and increasing the function of liver should be paid much more attention to. AA has remarkable effects of reducing blood lipid ^ antioxidation ^ apoptosis and preventing fatty degeneration, so it may prevent the formation and process of arteriosclerosis effectively and guard against myocardial ischemia.Section II Reaserch of the effect of Cyclovirobuxine-D onmyocardial ischemiaABSTRACTObjective To observe the effects of Cyclovirobuxine-D(CVB-D) on cardiac haemodynamics and experimental myocardial ischemia of anesthetic dogs, to compare the effect of Huangyangning tablet and CVB-D injection. Methods Myocardial ischemia of anesthetic dogs was induced with ligating coronary artery to investigate the effects of CVB-D. Carotid intubatton was used to observe the influence on hemodynamics, the myocardial infarction area, the content of serum CK and LDH of dogs. To compare the effect of Huangyangning tablet and CVB-D injection on myocardial ischemia.Result CVB-D could restrain the changes of left ventricular systolic pressure(LVSP), the maximum rising rate of left ventricular pressure(+dp/dtmax) - the maximum falling rate of left ventricular pressure(-dp/dtmax); change of left ventricular end diastolic pressure(LVEDP); changes of the myocardial infarction area and the content of serum creatine phosphokinase(CK) and LDH caused by ligating coronary artery were decreased. Compared to Huangyangning tablet at the same doseO.lmgkg"1), the remedial effect of CVB-D injection on hemodynamics is better and rapider.Conclusion CVB-D possessed protective effects on anesthetic dogs with experimental myocardial ischemia. Compared to Huangyangning tablet, the remedial effect of CVB-D injection on hemodynamics is better and rapider.