| Objective: Myocardial infarction is one of the most serious cardiovascular diseases and is associated with considerable morbidity, mortality and disability rate. Myocardial fibrosis(MF)is an important pathophysiological change after myocardial infarction, which can lead to ventricular dysfunction, irreversible arrhythmia, heart failure, even cardiogenic sudden death. MF after myocardial infarction istightly associated with the development and prognosis of the disease. The western medicine with MF treatment was mainly focused on angiotensin converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists and calcium antagonists. At present, there is no effective drug with little side reaction to suppress MF after myocardial infarction.Therefore, the treatment of MF after myocardial infarction is clinically urgent problem to be solved.Ginkgo biloba extract is a well-known traditional herb drug showing high physiological activity in therapies for diseases and is widely used more than 130 countries as a drug or food additive. The main active components of Ginkgo biloba extract are flavonoids and ginkgolides. Ginkgo biloba extract international standard is according to the German patent production of Ginaton(EGb761), which has 24% Ginkgo flavone glycosides, 6% ginkgo lactone and harmful substance ginkgoic acid less than 5?g/g. A large number of experiments showed that Ginkgo biloba extract EGb761 not only has a wide range of pharmacological activities, but also has the advantages of low-toxic side effect and wide-safe dose.Studies showed that Ginkgo biloba extract could significantly inhibit liver, kidney and lung fibrosis. For example, Ginkgo biloba extract EGb761 could suppress the activation of hepatic stellate cells and decrease the collagen secretion in the rat liver fibrosis. And EGb 761 could reduce the content of hydroxyproline in rat lung tissue of pulmonary fibrosis model. In rats with renal fibrosis, Ginkgo biloba extract could regulate the expression of angiotensin converting enzyme 2 to exert therapeutic effect. Our previous research found that Ginkgo biloba extract EGb 761 could significantly inhibit aldosterone induced cardiac fibroblasts proliferation and transformation in vitro, which indicated that Ginkgo bilobaextract has the potential to improve the occurrence and development of MF. However, the effect of Ginkgo biloba extract EGb 761 on the MF after myocardial infarction in vivo animal model need to be further confirmed.MF refers to excess deposition of extracellular matrix in myocardial tissue. Masson staining is easily to identify and evaluate the collagen fiber and connective tissue of MF by using hematoxylin, acid fuchsin and aniline blue. Hyaluronic acid(HA) widely distributed in extracellular matrix, connective tissue and organs, with its chemical nature of glycosaminoglycan. HA secreted increasely in the process of fibrosis, and then released into the circulation. Study showed that the level of HA in the blood was a noninvasive index reflecting the degree of MF. HA can be used as an important basis for observing the curative effect and prognosis of anti MF drugs.Therefore, the present study was undertaken to investigate the effect of Ginkgo biloba extract Egb761 on the MFafter myocardial infarction in rat model by observing the HA concentration and Masson staining. The aim was to study the effect of Ginkgo biloba extract on MF after myocardial infarction, and to provide theoretical and experimental basis for the prevention and treatment of MF after myocardial infarction.Method: Healthy male Sprague Dawley(SD) rats, body weight 260±20 g, from Center of Experiment Animal of Hebei Medical University, were randomly divided into the following 5 groups:1) Sham group: Rats in sham group underwent an identical surgical procedure without coronary ligation.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 TTC staining. After 4 weeks of drug administration, 5 rats from each group were anesthetized. The HA content in blood was detected using radioimmunoassay and the degree of MF was determined by Masson staining.Result:1 Cardiac morphology and TTC stainingIn the MF after myocardial infarction model group, the left ventricle anterior wall was thinner, grey and partly collapsed. The volume of the left ventricle was larger after 4 weeks. Ischemic region became pale and replaced by fibrous tissue. TTC staining showed that grey and white area was obvious in the rat myocardium in the model group,which indicated the area of MF after myocardial infarction. The results suggested that the MF after myocardial infarction animal model was successfully replicated in this study.2 Masson staining resultsIn the sham group, it was observed that myocardial fibers arranged in order, boundary clear and no inflammatory cell infiltration. However, normal cardiomyocytes replaced by disorderly arranged fibers, a massive inflammatory cell infiltrated, and occasionally island survival of cardiomyocytes were observed in the model group. MF after myocardial infarction was significantly reduced in model +EGb761 groups compared with model group. The higher dose of EGb761, the more obviously effect. EGb761 could decrease collagen fibers and inflammatory cell infiltration, as well as increase survival myocardial cells.3 Detection of HA in blood by radioimmunoassayRadioimmunoassay results showed that the HA content was significantly increased in the model group when compare with the sham group(P<0.01). Treated with three different doses of EGb761, the levels of HA in the blood were decreased obviously(P<0.01). The results indicated that Ginkgo biloba extract Egb761 could improve serum marker of fibrosis in MF after myocardial infarction rats.Conclusion:MF after myocardial infarction could successfully induced by permanent left anterior descending coronary artery ligation, and the degree of MF could significantly reduce by EGb761 in rats. The HA content was significantly increased in the model group, while Ginkgo biloba extract Egb761 could significantly improve the change of HA content. |
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