Protective Effects And Mechanisms Of Guanxin Ⅱ On Myocardial Ischemia

GuanxinⅡis a compound made from Chinese herbs of Radix Salviae Miltiorrhizae(丹参),Rhizoma Chuanxion(川芎),Radix Paeoniae Rubr(赤芍), Flos Cartham(红花),Lignum DalbergiaeOdorifera(降香)basing on the theory of traditional Chinese medicine.This compound has many functions such as relieving blood stasis,promoting blood circulation and relieving pain.Clinical observations have confirmed that GuanxinⅡcan increase the patient's coronary circulation index,improve coronary blood supply.Animal experimental studies had confirmed GuanxinⅡhas many pharmacological effects on heart such as enhancing heart function and improving myocardial ischemia,preventing aggregation of platelets and formation of thrombosis.To investigate the protective effects and mechanisms of GuanxinⅡon myocardial ischemia injury with the establishment of acute myocardial infarction model and myocardial ischemia-reperfusion model in rats.1 The protective effects of GuanxinⅡon acute myocardial infarction in ratsObjective:To observe the effects of GuanxinⅡon myocardial enzyme, myocardial injury degree,myocardial apoptosis and myocardial free radicals of acute myocardial infarction in rats,so as to explore the effects and mechanisms of GuanxinⅡon acute myocardial ischemia.Methods:The rats were divided randomly into three groups:GuanxinⅡgroup,control group and model group. Administrated standard decoction of GuanxinⅡto rats with the dosage of 10g·kg^-1or normal saline for 7 d.Then set up model of acute myocardial infarction by ligated the left descending coronary artery(LAD)of heart.24 hours after acute myocardial infarction,blood and myocardial tissues were taken.(1)The activities of LDH,AST,CK and CK-MB in serum were measured by colorimetry.(2)Degree of myocardial pathology injury was observed by light microscopy.(3)Myocardial ultrastructure was observed by electron microscope. (4)Apoptosis in the myocardial ischemic area was observed by TUNEL.(5)The content of MDA,activities of SOD and GSH-PX were measured by colorimetry. Results:(1)Compared with control group,the activities of LDH,AST,CK and CK-MB increased significantly in model group;Compared with model group, the activities of CK,CK-MB,LDH and AST decreased significantly in GuanxinⅡgroup.(2)In light microscope,the myocardial fiber arranged in disorder,high edema in interstitial,myocardial necrosis with infiltration by a large number of inflammatory cells;Compared with model group,pathological injury of GuanxinⅡgroup reduced significantly.(3)In electron microscope, mitochondrias swelled generally in model group,ridges of mitochondria became short,scare and arranged irregularly;ridges in some mitochondrias even disappeared;mitochondrial structure significantly improved in GuanxinⅡgroup.(4)Compared with control group,the number of apoptosis cells was higher both in GuanxinⅡgroup and mode group,but the number of apoptosis cells was lower in GuanxinⅡgroup.(5)Compared with control group,content of MDA was increased,activities of SOD and GSH-PX decreased significantly in model group;Compared with model group,content of MDA was reduced, activities of SOD and GSH-PX increased significantly in GuanxinⅡgroup. Conclusion:GuanxinⅡcan reduce activities of LDH,AST,CK and CK-MB, necrosis in ischemic myocardial cells,infiltration of inflammatory cells and damage of ischemic myocardial mitochondrial has protective effects on ischemic myocardial cells.The possible mechanisms may be related to reducing myocardial apoptosis,improving antioxidant capacity and protecting myocardial mitochondria.2 The protective effects of GuanxinⅡon myocardial apoptosis of myocardial ischemia-reperfusion model in ratsObjective:To observe the effects of GuanxinⅡon myocardial apoptosis, expressions of myocardial Bax,Bcl-2 protein and Caspase-3 mRNA of myocardial ischemia-reperfusion model in rats,so as to explore the effects and mechanisms of GuanxinⅡon myocardial apoptosis.Methods:The rats were divided randomly into three groups:GuanxinⅡgroup,control group and model group.Administrated standard decoction of GuanxinⅡto rats with the dosage of 10g·kg^-1or normal saline for 7 d.Then set up model of myocardial ischemia-reperfusion by ligated the coronary artery of rat heart for 30 min and then reperfused 60 min.(1)Myocardial apoptosis in ischemic area was observed by TUNEL.(2)Bax and Bcl-2 protein expressions were checked by immunohistochemistry.(3)Expression of Caspase-3 mRNA of myocardial cells were detected by fluorescence quantitative PCR.Results:(1)Compared with control group,the number of apoptosis cells was higher in GuanxinⅡgroup and model group,but the number of apoptosis cells in GuanxinⅡgroup was lower than model group.(2)Compared with control group,Bax and Bcl-2 protein expressions increased significantly in model group but the Bcl-2/Bax ratio decreased;Compared with model group,the expression of Bcl-2 increased, but the expression of Bax decreased in GuanxinⅡgroup,the Bcl-2/Bax ratio increased.(3)Compared with control group,Caspase-3 mRNA expression increased in model group and GuanxinⅡgroup,but Caspase-3 mRNA expression was lower in GuanxinⅡgroup than model group.Conclusion: GuanxinⅡcan reduce myocardial apoptosis of myocardial ischemia-reperfusion in rats to protect injury from myocardial ischemia-reperfusion.The possible mechanisms may be related to up-regulating Bcl-2 protein expression,down-regulating Bax protein expression and Caspase-3 mRNA expression.To sum up,GuanxinⅡhas the protective effects on myocardial ischemia by reducing myocardial apoptosis,increasing antioxidant capacity and protecting myocardial mitochondria;GuanxinⅡcan up-regulate the Bcl-2 protein expression,down-regulate the expression of Bax protein and Caspase-3 mRNA, so as to inhibit myocardial apoptosis of myocardial ischemia-reperfusion.