Studies On The Pharmacodynamics Of HUANGDANLAN Granules(2)

Objective: Through the observation of animal experiment on myocardial protective effect of HUANGDANLAN Granules,explore the efficacy study of HUANGDANLAN Granules in the treatment of atherosclerosis,myocardial hypertrophy and other heart diseases,verify the therapeutic effect of the drug in the clinic,to provide experimental basis for clinical medicine.Methods: Through the determination of the release of PGI2 in normal rat arterial rings without drug preconditioning and the release of PGI2 in normal rat arterial rings pretreated with HUANGDANLAN Granules,observe the impact of HUANGDANLAN Granules on platelet aggregation and blood vessel environmental;Through the establishment of rat model of myocardial infarction,the cross section of heart were Masson stained to determinate CVF and detect TNFprotein expression by Western blot method,observe the influence of HUANGDANLAN Granules on myocardial fibrosis and myocardial tissue remodeling in rats with TNF-? expression;The establishment of rat model of myocardial hypertrophy induced by ISO,determinate the protein content in myocardial cells,myocardial cell volume,the Ca²⁺ concentration detection of myocardial and ANP mRNA expression by RT-PCR method,to observe the protective effect of HUANGDANLAN Granules on myocardial hypertrophy induced by ISO in neonatal rats;By establishing the model of myocardial ischemia,determinate the serum CK,LDH,AST activity of myocardial ischemia in rats,and myocardial SOD activity,MDA content,observe the protective effect of HUANGDANLAN Granules on myocardial ischemia;Through the establishment of hypoxia-reoxygenation model myocardial model,study on electrophysiological function and energy metabolism in myocardial cells,to investigate the protective effect of HUANGDANLAN Granules on myocardial injury induced by hypoxia-reoxygenation model;To study the effect of HUANGDANLAN Granules on the release of VW and prostacyclin in the blood vessel wall of the umbilical vein,and to study the effect of HUANGDANLAN Granules on promoting blood circulation,anticoagulation and thrombosis.RESULTS: The normal dose HUANGDANLAN Granules can maintain the stability of PGI2 in the rat arterial wall,maintain its normal activity,and is favorable to stabilize the vascular environment,but when normal rats artery ring treated with a large doses of HUANGDANLAN Granules,compared to the results of the activity of PGI2 arterial rings under the normal environment was very significant difference,suggesting that large doses of HUANGDANLAN Granules medication can inhibit the arterial wall to generate PGI2,decreased the activity of PGI2,make an adversely affect on the expansion of blood vessels,blood platelet aggregation,antagonistic and prevent myocardial remodeling and cardiac hypertrophy;with the increase of the dose of HUANGDANLAN Granules observe the Masson staining results,the degree of myocardial fibrosis was significantly improved compared with the model group,the ventricular remodeling after infarction cardiac change,CVF decreased significantly,and the difference is significant?P<0.01?.Through the determination of the expression of TNF-? protein in rat myocardium,the results showed that with HUANGDANLAN high dose group,the expression level of TNF-? protein in rat cardiomyocytes was the lowest,with significant difference?P<0.01?;To establish the models of myocardial hypertrophy induced by ISO successfully,protein content,cardiomyocyte hypertrophy cell size and protein expression level were decreased after using the HUANGDANLAN Granules,there was significant difference?P< 0.01?,while the performance results and the dosage in a dose-dependent manner,in addition,the results showed that HUANGDANLAN Granules also reduced the concentration of Ca²⁺ in hypertrophic cardiomyocytes,which was significantly different from that in the blank group?P<0.01?;through the administration of HUANGDANLAN Granule in rats injected with myocardial ischemia model,determination of myocardial ischemia on rat serum CK,LDH,AST and the activity of SOD and MDA,the content of MDA increased significantly in the model group,SOD activity decreased,myocardial cells were severely damaged,cells mortality increased,oxygen free radicals and lipid peroxidation in myocardium increased strongly.While the HUANGDANLAN Granules administration can significantly reduce the granules in serum of rats with acute myocardial ischemia on LDH,CK,AST;at the same time also can reduce the content of MDA in serum,increase the activity of SOD;After hypoxia reoxygenation injury of myocardial cells,Na⁺,K⁺-ATPase,Ca²⁺,Mg²⁺-ATPase concentrations were decreased,after administration of HUANGDANLAN Granules,Na⁺,K⁺-ATPase,Ca²⁺,and Mg²⁺-ATPase content increased significantly,compared with the model group,the difference was significant?P<0.05 or P<0.01?,at the same time in a dose-dependent manner,with the increase of the dosage,the content of Na⁺,K⁺-ATPase,Ca²⁺,Mg²⁺-ATPase obviously increase.At the same time the content of injury in myocardial cells of ATP have high sensitivity to HUANGDANLAN Granules,especially for the HUANGDANLAN Granules administration of a high dose of granules,the content of ATP increased,the protective effect is most obvious,significant difference?P<0.05?;perfusion in fresh umbilical vein,and in perfusion join HUANGDANLAN liquid drug granules,determination of factor VW and prostacyclin activity,the inhibition of HUANGDANLAN perfusate on the VW factor is obvious,and has little influence on the release of prostacyclin.Conclusions: PGI2 is an important factor in vascular smooth muscle cells,the proper dose of HUANGDANLAN Granules can be maintained in PGI2 synthesis,artery release,its activity can dilate blood vessels,improve myocardial state,antagonizing myocardial remodeling,effective treatment of myocardial hypertrophy and other symptoms,however,there is no relationship between the intensity and dose,when the dose is increased,the effect is weakened,so we need to choose the appropriate dose treatment;HUANGDANLAN Granules can help the myocardial fibrosis and ventricular remodeling in myocardium by reducing CVF and the expression of TNF-?,which has important significance for improving myocardial hypertrophy and inhibit the inflammatory expression,and the strength of the effect and dose related positively;HUANGDANLAN Granules can inhibit the hypertrophy of myocardial cells induced by ISO,decrease the content of protein and ANP mRNA expression in hypertrophic myocardium,and decrease the volume of myocardial cells,and is positively correlated with the measurement,indicating that the protective effect of HUANGDANLAN Granules has slowed down and reversed on myocardial hypertrophy.At the same time,HUANGDANLAN Granules also reduced the concentration of Ca²⁺ in hypertrophic cardiomyocytes,suggesting that the channel to prevent myocardial hypertrophy may be to inhibit the concentration of calcium Ca²⁺ in hypertrophic cardiomyocytes;HUANGDANLAN Granules protect the activity of SOD by improving the ability of scavenging oxidative substances,reduce myocardial oxidative injury,against heart damage on the myocardial ischemia,and thus play a role in myocardial protection;HUANGDANLAN Granules can protect against myocardial injury induced by myocardial ischemia and protect the heart.HUANGDANLAN Granules effective oxygen on myocardial injury in hypoxia reoxygenation,improve electrophysiological function,can effectively increase the content of ATP in myocardial cells,regulating energy metabolism,help restore normal function level,alleviate the myocardial injury due to hypoxia and the clinical curative effect is very considerable;The inhibitory effect of HUANGDANLAN perfusate on VW factor was obvious,which indicated that HUANGDANLAN Granules had certain effects of promoting blood circulation and thrombosis.HUANGDANLAN Granules had anticoagulant activity.The inhibition of VW release may be one of the mechanisms of promoting blood circulation and antithrombosis.