| Objective: Cardiovascular disease is the leading cause of death worldwide and is associated with high morbidity,disability and poor quality of life.Myocardial infarction is one of the most serious cardiovascular diseases.Fortunately,the treatment of acute myocardial infarction is more and more advanced worldwide,which save many lives.However,patients that survive an acute myocardial infarction may subsequently suffer myocardial fibrosis,which characteristic pathological alterations are cardiac fibroblasts proliferation,myocyte hypertrophy,collagen synthesis increase and excessive deposition.Myocardial fibrosis could lead to ventricular systolic and diastolic dysfunction,arrhythmia,heart failure and even sudden cardiac death.There is no effective treatment with myocardial fibrosis after myocardial infarction and to improve the life quality.Therefore,it is important to study the mechanism and prevention of myocardial fibrosis after myocardial infarction to improve the survival rate and prognosis of patients.Ginkgo biloba extract(GBE)is the standardized extract of Ginkgo biloba leaves,the compounds are flavonoids and terpenoid lactones,a small amount of organic acid and alkyl phenol,etc.Research indicated that GBE has many positive effects,such as scavenging radicals,anti-oxidation,improving blood rheology,anti-platelet aggregation and preventing atherosclerosis.In addition,GBE could ameliorate liver fibrosis and function via reduce the expression of ?-smooth muscle actin,transforming growth factor-? and collagen I in the rat liver tissue.At the same time,GBE could improve the clinical symptoms of patients with pulmonary fibrosis,regulate pulmonary function and reduce the expression of tumor necrosis factor,which indicated that GBE may have therapeutic effect on pulmonary fibrosis.Our previous studies showed that GBE could obviously inhibit aldosterone induced cardiac fibroblasts proliferation and transformation,which suggested that GBE may improve myocardial fibrosis.However,the effect of GBE on the myocardial fibrosis after myocardial infarction in rat model need to be further confirmed.This experiment use the international standard of GBE,namely by the German patent production of Ginaton(EGb 761),which has the advantages of low toxic side effect and wide safe dose.Collagen proliferates in the process of myocardial fibrosis,and myocardial collagen consists mostly of collagen type I and ?.N-terminal propeptide of procollagen ?(P?NP)can be found circulating in the bloodstream,and has been used as peripherally measurable marker of myocardial fibrosis.In addition,studies have shown that P?NP is well known for its excellent storability and stability,and low between subject variability.Interestingly,P?NP produced the most striking results,compared to the other collagen biomarkers.Therefore,this study was designed to examine the effect of different doses of GBE on the myocardial fibrosis after myocardial infarction in rat model by observing the change of P?NP in blood and pathological changes of myocardial tissue.The aim was to study the effect of GBE on myocardial fibrosis after myocardial infarction,to provide theoretical and experimental basis for the prevention and treatment of myocardial fibrosis after myocardial infarction,and promote the development of Chinese medicine against myocardial fibrosis.Methods: Healthy male Sprague Dawley rats,weight 260±20 g,from Hebei medical university animal center,were randomly divided into the following five groups:1)Sham group: The sham-operated animals underwent the same procedure except that the silk suture was placed around the left coronary artery without being tied.2)Model group: Myocardial infarction was induced by permanent left anterior descending coronary artery ligation,and rats treated with normal saline.3)Model + EGb 761(25 mg/kg)group: Myocardial infarction was induced by permanent left anterior descending coronary artery ligation,and rats treated with EGb 761 25 mg/kg/day.4)Model + EGb 761(50 mg/kg)group: Myocardial infarction was induced by permanent left anterior descending coronary artery ligation,and rats treated with EGb 761 50 mg/kg/day.5)Model + EGb 761(100 mg/kg)group: Myocardial infarction was induced by permanent left anterior descending coronary artery ligation,and rats treated with EGb 761 100 mg/kg/day.If a rat died in the process,another animal filled.After 4 weeks,3 rats from model group were obtained to evaluate the model condition by 2,3,5-triphenyltetrazolium chloride(TTC)staining.After 4 weeks of drug administration,5 rats from each group were anesthetized.The P?NP content in blood was detected using radioimmunoassay and myocardial tissue pathological change was determined by HE staining.Results:1 The heart shape and TTC staining results:In the myocardial fibrosis after myocardial infarction model group,the rats were anesthetized 4 weeks after operation and hearts were observed the change of the gross appearance and TTC staining.The volume of the left ventricle was larger and the left ventricle anterior wall was thinner,grey and partly collapsed.Ischemic region was replaced by fibrous tissue.TTC staining showed that normal myocardial tissue was vivid red,and fibrotic myocardium was white discoloration.Obvious gray areas could be observed in the left ventricular wall of model rats,and red area in right ventricular.Results indicated that left anterior descending coronary artery ligation could successfully copied model of myocardial fibrosis after myocardial infarction in rats.2 Myocardial tissue HE staining results:HE staining showed that myocardial fibers arranged regularly,no inflammatory cell infiltration in the sham group.While infarcted myocardium was replaced by disorderly arranged fibers,and a massive inflammatory cell infiltrated in myocardial fibrosis after myocardial infarction model group,which indicated the model was successful.In model + EGb 761 groups,three different doses of GBE could significantly relieve myocardial tissue pathological changes.The bigger GBE dose,the more myocardial cells survived,and the less collagen fibers and inflammatory cells.Results showed that GBE could improve pathological changes in rat myocardial fibrosis after myocardial infarction.3 Detection of P?NP content in blood by radioimmunoassay:Radioimmunoassay results showed that P?NP content was significantly increased in the model group when compare with sham group(P<0.05).Which indicated that model group increased level of blood marker of myocardial fibrosis in rats.In addition,treated with three different doses of GBE,P?NP content in the blood were significantly decreased in the model + EGb 761 groups(P<0.05).Results demonstrated that GBE could improve the blood marker of myocardial fibrosis after myocardial infarction in rats.Conclusion: Left anterior descending coronary artery ligation could result in significant myocardial fibrosis after myocardial infarction in rats,and GBE could improve pathological changes of myocardial fibrosis in rats after myocardial infarction.The P?NP content was significantly increased in rats of myocardial fibrosis after myocardial infarction,while GBE could obviously improve the change of P?NP content. |
PDF Full Text Request