Protective Effects And Mechanisms Of Ginsenoside-Rg1 On The Acute Myocardial Ischemia In Rats

Objective:The effects and mechanisms of ginsenoside-Rg1 were studied in the acute myocardial ischemia of rats. In the present study, we observed whether ginsenoside-Rg1 could reduce the infarcted area and improve the injury induced by ischemia in myocardial ultrastructure. We investigated the mechanisms of ginsenoside-Rg1, mainly including the molecular mechanism of Rg1-induced angiogenesis and the mechanism of antioxidant effects of ginsenoside-Rg1 on the acute myocardial ischemia in rats.Methods:Wistar rats were divided randomly into the sham operation group, the model group, MET (4.5mg·kg-1) group, Rg1 a (5mg·kg-1) group, Rg1 b (10mg·kg-1) group, Rg1 c (15mg·kg-1) group. The acute ischemia model was made by ligating the left anterior descending branch of coronary artery in rats. The rats were anesthetized and taken the blood and the heart after the drug be administrated for 14 days. The myocardial infarction area were measured after 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The myocardial ultrastructure was observed by electronmicroscope. Vascular endothelial cells were stained by immunohistochemistry staining, which was used to examine myocardial microvessel density (MVD). The growth of microvessels was observed by counting the number of newly formed micovessels using microscope. Immunohistochemistry staining was used to examine the protein expression of myocardial VEGF, VEGFR1, VEGFR2 and p-Akt. Spectrophotometry was used to examine myocardium nitric oxide levels. Spectrophotometry was used to examine serum superoxides dismutase (SOD), glutathione peroxidase (GSH-Px), malomdialdehyde (MDA).Results:Ginsenoside-Rg1 was shown to have protective effects on myocardial ischemia in rats. Compared with the model group, The infarct area was reduced obviously by ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) in the acute myocardial ischemia of rats (P<0.01, P<0.001). Ginsenoside-Rg1 (5, 10 mg·kg-1 i.p.) could ameliorate the change induced by ischemia in myocardial ultrastructure. So it can relieve the injury induced by the acute myocardial ischemia in rats. The mechanisms of protective effects of ginsenoside-Rg1 were as follows:Ⅰ.The angiogenesis was induced by ginsenoside-Rg1.Compared with the model group, Ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) could increase obviously microvascular vascular density (MVD) in ischemic myocardium (P<0.01). Ginsenoside-Rg1 (10mg·kg-1 i.p.) could increase the protein expression of myocardial VEGF by Immunohistochemistry staining (++). Ginsenoside-Rg1 (15mg·kg-1 i.p.) could increase obviously the protein expression of myocardial VEGF by Immunohistochemistry staining (+++). Ginsenoside-Rg1 (10mg·kg-1 i.p.) could increase the protein expression of myocardial VEGFR1 and VEGFR2 by Immunohistochemistry staining (++). Ginsenoside-Rg1 (15mg·kg-1 i.p.) could increase obviously the protein expression of myocardial VEGFR1 and VEGFR2 by Immunohistochemistry staining (+++). Compared with the model group, Ginsenoside-Rg1 (10mg·kg-1 i.p.) could increase the protein expression of myocardial p-Akt by Immunohistochemistry staining (++). Ginsenoside-Rg1 (15mg·kg-1 i.p.) could increase obviously the protein expression of myocardial p-Akt by Immunohistochemistry staining (+++). Compared with the model group, Ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) could increase obviously the content of myocardium nitric oxide (P<0.05, P<0.01). Therefore, The effect of ginsenoside-Rg1 on angiogenesis may be realized through VEGF—VEGFR1, VEGFR2—Akt—NO signal pathway.Ⅱ. Ginsenoside-Rg1 was shown to have antioxidant effects. Compared with the model group, Ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) could increase obviously the activity of SOD in serum (P<0.05, P<0.01). Ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) could increase obviously the activity of GSH-Px in serum (P<0.01, P<0.001). Compared with the model group, Ginsenoside-Rg1 (10, 15 mg·kg-1 i.p.) could decrease obviously the content of MDA in serum (P<0.05).Conclusion:Ginsenoside-Rg1 was shown to have protective effects on myocardial ischemia. It can reduce the infarct area and ameliorate the change induced by ischemia in myocardial ultrastructure on the acute myocardial ischemia in rats. The mechanisms of protective effects of ginsenoside-Rg1 were as follows: Ginsenoside-Rg1 induced angiogenesis in ischemic myocardium. The molecular mechanisms of ginsenoside-Rg1 on angiogenesis may be correlated with VEGF—VEGFR1, VEGFR2—Akt—NO signal pathways. Another mechanisms of protective effects of myocardium is that ginsenoside-Rg1 has the antioxidant effects. It can increase the activity of SOD and GSH-Px in serum, and decrease the content of MDA in serum.