The Experimental And Clinical Research On Protective Effect And Mechanism Of Sofren On Myocardial Ischemia-Reperfusion Injury

Purpose:The aim of the study is to make a thorough inquiry on the protective effect of salidroside on rats with myocardial ischemia-reperfusion injury,and is also to explore its mechanism and provide a scientific and objective basis for myocardial ischemia-reperfusion injury by using Chinese medicine.Methods:Healthy male SD rats/weight240±10g。Myocardial ischemia-reperfusion model was produced in rats by ligation of the left anterior descending coronary artery. Randomly divided into6groups:sham operation group (S group), ischemia-reperfusion group(I/R group),salidroside preventive group(first treating with salidroside and then inducing ischemia-reperfusion) and salidroside treatment group (first inducing ischemia-reperfusion and then treating with salidroside), salidroside preventive+LY294002group, salidroside treatment+LY294002group,6rats in each group. Coronary artery in rats of sham operation group was not ligated but weared wire,directly off the chest,while the left anterior descending(LAD) of coronary artery in rats of the other groups was ligated for30min.Then cut the ligature, to restore blood flow and recanalize coronary, myocardial ischemia-reperfusion model was produced. Close the chest after ECG to be stable10minutes later. Successful ligation iconic performance:ST segment move up, QRS wave shape appears left bundle branch block kind of large abnormal,left ventricular anterior local color pale or cyanotic. Signs of coronary recanalization performance:ST segment elevation relative decline in more than50%, QRS amplitude becomes narrow and low, pale or cyanotic ischemic area of the color turned red. Both of the salidroside preventive group and salidroside preventive+LY group administered continuously modeling three days before, once a day, Salidroside12mg/kg intraperitoneal injection; salidroside treatment group and salidroside treatment+LY group in addition to the immediate reperfusion,Salidroside intraperitoneal injection of12mg/kg. The salidroside preventive+LY group and treatment+LY group with an additional injection of PI3K inhibitor(LY294002)0.3mg/kg intraperitoneal injection slowly10min before operation. Those were given medicines via intraperitoneal injection at the beginning of reperfusion. Rats in sham operation group and ischemia-reperfusion group(I/R group) received a same volume of0.9%NaCl. Then collecting blood samples from abdominal artery, to inspect Serum myocardial enzymes.Enzyme-linked immuno sorbent assay method was used to measure the levels of serum cardiac damage biomarkers(cTnI and CK-MB). Evans blue and TTC staining were used to evaluate the extent of myocardial infarction.Myocardium apoptosis rate was measured by TUNEL. The levels of pAKT and p-GSK3-b protein wee detected by western-bloting.Results:1. The sham group had lower serum CK-MB, CTnT, myocardial infact size and apoptosis index level than othergroups, and there was no ischaemic or necrotic area.(P<0.01).2.Compared with I/R group, the level of CK-MB and CTnT decreased significantly in both salidroside preventive and treatment groups (P<0.05), while myocardial infact size reduced(P<0.05) and the apoptosis index lower (P<0.01).3.Compared with salidroside preventive group, preventive+LY group serum CK-MB and CTnT activity increased, myocardial infact size increased, apoptosis index increased(P<0.01).4.Compared with salidroside treatment group, treatment+LY group serum CK-MB and CTnT activity increased, myocardial infact size increased, apoptosis index increased(P<0.01).5.Compared with salidroside preventive group and treatment group, there is no significant difference of the level of CK-MB and CTnT, myocardial infact size and the apoptopsis index(P>0.01).Conclusions:Salidroside plays a protective role in rats with MIRI. Its mechamism may involve in reducing oxygen free radicals,reducing markedly the release of CK-MB and CTnT independ of concentration and inhibit the myocardial apoptosis. Salidroside protects cardiomyocytes from I/R-induced apoptosis through PI3K/AKT/GSK-3b signaling pathway. Purpose:Making a thorough inquiry through clinical randomized controlled study on the protective effect of "Sofren Injection" on patients with myocardial ischemia-reperfusion injury, and is also to investigate possible mechanism and provide a scientific basis for myocardial ischemia-reperfusion injury by using Chinese medicine.Methods:The therapy (PCI) in patients2013.12-2014.4in Nanjing Military Region General Hospital and the Hospital of Jiangsu Province, has been hospitalized as a research object coronary intervention.Select80patient. Western diagnostic criteria and the patient TCM is consistent with blood stasis type randomly divided into control group (20cases), large strains Rhodiola injection treatment group (30cases) and salvianolate injection treatment group (30patients). All groups were treated with normal western medical therapy according to the guideline:enteri coated aspirin Lin, clopidogrel,low molecular weight herparin,nitrates,ACEI and ARB, b-receptor blockers,necessary blood pressure and hypoglycemic therapy. Sofren Injection treatment group needs Sofren Injection sodiumeach10ml,once daily;the salvianolate injection also requires intravous injection fleabane,each0.2g,once a day.The course is about3-7days.Using any other Chinese medicine during the treatment is prohibitted. In the case of revascularization before surgery, three days take peripheral blood serum5ml were detected, preparation, analysis and comparison of detection of myocardial enzymes, cardiac markers, glucolipid metabolism,IL-6、TNF、CRP、SOD and NO index.Result:1.reducing oxidation role:the treatment group compared with the control group, SOD and NO was decreased after PCI treatment group, SOD and NO patients decreased less than patients in the control group, the comparison between the two significantly different (P<0.05).2.The anti-inflammatory effects:the medicine group and the control group, increased CRP IL-6,CRP and TNF level after PCI, the elevated level of medication groups of patients with IL-6,CRP and TNF than patients in the control group, the comparison between the two significantly different (P<0.05).Conclusion: 1. Through observation of clinical cases confirmed, on the basis of conventional therapy plus sofren injection or sodium phosphocreatine, can relieve the syndrome patients with PCI after myocardial ischemia reperfusion injury of acute coronary artery, and its mechanism may be related with inhibiting the inflammatory response,scavenging oxygen free radicals and others.It can be used in clinical practice.3.There is no significant difference between Sofren Injection and salvianolate injection for patients with myocardial ischemia-reperfusion injury. Its curative effect is better than that of single western medicine treatment.