Research On Protective Effect Of Timosaponin On Myocardial Ischemia And Its Mechanism

Objective To research the protective functions and mechanism of timosaponin Officinalisi-nin I and timosaponin b II by intragastric administration method on myocardial ischemia.To research the protective functions and mechanism of timosaponin Officinalisi-nin I by intraperitoneal injection method on myocardial ischemia.Methods(1)The rats were randomly divided into 7 groups:blank control group,model group,high Officinalisinin ? group,low Officinalisinin ? group,high timosaponin b II group,low timosaponin b II group and positive group.Acute myocardial ischemia rat models were made with Isoproterenol.Each treated group ig Officinalisinin ?(300mg/kg,600mg/kg)and timosaponin b II(300mg/kg,600mg/kg)and DK(positive group,120mg/kg).the rats had been intragastrically administered daily for five days.We observed the pathological changes of myocardial tissue,tested CK,LDH,AST level in serum.(2)The rats were randomly divided into 5 groups:blank control group,model group,high Officinalisinin ? group,low Officinalisinin ? group and positive group.Acute myocardial ischemia rat models were made with Isoproterenol.Each treated group ig Officinalisinin ?(300mg/kg,600mg/kg)and DK(positive group,120mg/kg).the rats had been intragastrically administered daily for five days.We tested changes of Gsh-px?SOD?ROS?MDA;Bcl-2?BAX?p53 and HO-1 in myocardial tissue.(3)The rats were randomly divided into 6 groups:blank control group,model group,high Officinalisinin ? group,mid Officinalisinin ? group,low Officinalisinin ? group and positive group.Acute myocardial ischemia rat models were made with Isoproterenol.Each treated group was administered by intraperitoneal injection of Officinalisinin ?(100mg/kg,50mg/kg,25mg/kg)and DK(positive group,100mg/kg).The rats had been intragastrically administered daily for five days.We observed the pathological changes of myocardial tissue,tested CK,LDH,AST level in serum.And also,we tested changes of Gsh-px?SOD?ROS?MDA;Bcl-2?BAX?p53 and HO-1 in myocardial tissue.We tested apoptosis in myocardial tissue by tunel method.Results:(1)Both officinalisinin ? and timosaponin b? can improve the pathological changes of the myocardial ischemia model and reduce the level of LDH,CK,AST in the serum of the myocardial ischemia model by intragastric administration.Compare to timosaponin b? group;officinalisinin ? group has a bigger reduction on LDH?CK?AST level.(2)Officinalisinin ? by intragastric administration can reduce the level of MDA,ROS in the myocardial ischemia model and increase the activity of the Gsh-px and SOD.Officinalisinin ? by intragastric administration can reduce the level of Bax and p53 in the myocardial ischemia model and increase the level of Bcl-2 and Bcl-2/Bax value in the myocardial tissue.Officinalisinin ? has no obvious impact on the level of HO-1 protein in the myocardial ischemia model.(3)Officinalisinin ? by intraperitoneal injection can improve the pathological changes of the myocardial ischemia model and reduce the level of LDH,CK,AST in the serum of the myocardial ischemia model.Officinalisinin ? by intraperitoneal injection can reduce the level of MDA,ROS in the myocardial ischemia model and increase the activity of the Gsh-px and SOD.It also has anti-apoptosis effect.Officinalisinin ? by intraperitoneal injection can reduce the level of Bax and p53 in the myocardial ischemia model and increase the level of Bcl-2 and Bcl-2/Bax value in the myocardial tissue.Compare to Officinalisinin ? by intragastric administration,Officinalisinin ? by intraperitoneal injection has a much smaller effective dose on protective effect of myocardial ischemia.Conclusions:(1)Officinalisinin ? and timosaponin b? both have protective effect for the injury of myocardial ischemia.And compare to timosaponin b?,Officinalisinin ? is more effective on myocardial ischemia.(2)Officinalisinin ? by intragastric administration can reduce the level of MDA,ROS in the myocardial ischemia model and increase the activity of the Gsh-px and SOD.It shows that Officinalisinin ? can protect myocardial tissue by against free radical and over-oxidation.It also has anti-apoptosis effect,its mechanism is related to the improvement of apoptosis protein of myocardial cells.Officinalisinin ? has no obvious impact on the level of HO-1 protein,which shows that its functions have no relationship with HO-1 protein.(3)Officinalisinin ? by intraperitoneal injection also has protective effect for the injury of myocardial ischemia.its mechanism is related to the improvement of apoptosis protein of myocardial cells,against free radical and over-oxidation.Compare to Officinalisinin ? by intragastric administration,Officinalisinin ? by intraperitoneal injection has much fewer effective dose.The reason maybe is by intraperitoneal injection method has higher bioavailability than intragastric administration method.