Objective To explore the protective effect of L-carnitine on the reperfusion injury of rat heart transplantation. Methods The rat model of cervical heterotopic heart transplantation was set up. L-carnitine was injected to acceptor 4h before transplantation. Myocardiac malondialdehyde(MDA) and superoxide dismutase(SOD) concentrations were measured 2h after reperfusion. Pathological change of myocardium, especially mitochondria, was detected by transmission electronic microscope. Apoptosis of myocardial cells was determinded by TUNEL. Results Myocardial MDA concentration in L-carnitine treatment group was significantly lower than that in control group (P

Objective To investigate the cardioprotective effects of 3-nitropropionic acid (3-NPA) pretreatment against ischemia-reperfusion (I/R) injury. Methods Sixteen male Wistar rats weighing 200-250 g were randomly divided into 2 groups ( n = 8 each):(1) 3-NPA group received intraperitoneal 3-NPA 4 mg?kg-1 24 h before the animals were sacrificed and (2) control group received normal saline instead of 3-NPA. The animals were sacrificed and the hearts were immediately removed and mounted on Langendorff apparatus and perfused with K-H solution saturated with 95% O2 and 5% CO2 at 37℃ . After being perfused for 30 min the hearts were subjected to 30 min global ischemia by suspension of perfusion followed by 60 min reperfusion. The HR, left ventricular developed pressure (LVDP) and ? dp/dtmaxd were recorded before ischemia and at 30 and 60 min of reperfusion. Coronary effluent was collected at 15 min of reperfusion for determination of CK and LDH activity. At the end of 60 min reperfusion the hearts were removed for determination of myocardial MDA content and SOD activity.Results LVDP and ? dp/dtmax recovered significantly better in 3-NPA group than in control group. The myocardial MDA content, CK and LDH release were significantly lower in 3-NPA group than in control group. The myocardial SOD activity was significantly higher in 3-NPA group than in control group. Conclusion Chemical preconditioning with 3-NPA protects the heart from I/R injury.

The effects of oxidized low density lipoprotein (ox-LDL) on the proliferation of cultured human vascular smooth muscle cells (vSMC) were investigated in vitro. By using NaBr density gradient centrifugation, LDL was isolated and purified from human plasma. Ox-LDL was produced from LDL by being incubated with CuSO(4). ox-LDL was then added to the culture medium at different concentrations (35, 60, 85, 110, 135 and 160 microg/mL) for 7 days. The influence of ox-LDL on vSMC proliferation was observed in growth curve, mitosis index, and in situ determination of apoptosis. The data were analyzed with SPSS 10.0 software. The results showed that the ox-LDL produced in vitro had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque. ox-LDL at a concentration of 35 microg/mL demonstrated the strongest proliferation inducement, and at a concentration of 135 microg/mL, ox-LDL could inhibit the growth of vSMC. ox-LDL at concentrations of 35 and 50 microg/mL presented powerful mitotic trigger, and with the increase of ox-LDL concentration, the mitotic index of vSMC was decreased gradually. ox-LDL at higher concentrations promoted more apoptotic vSMCs. ox-LDL at lower concentrations triggered proliferation of vSMCs, and at higher concentrations induced apoptosis in vSMCs. ox-LDL played a promotional role in the pathogenesis and development of atherosclerosis by affecting vSMC proliferation and apoptosis.

The effects of stromal-derived factor 1 preconditioning (PC) on apoptosis of bone mesenchymal stem cells (BMSCs) treated with hypoxia plus serum deprivation were investigated. Bone mesenchymal stem cells were cultured with the whole marrow-adherence technique. RT-PCR and immunohistochemistry were used to detect the expression of CXCR4. BMSCs were incubated in medium for 24 h with 10 ng/mL and 100 ng/mL SDF-1 respectively, and then they were treated with hypoxia plus serum deprivation for 6 h. Apoptosis rate was determined by flow cytometry and TUNEL method. The results showed that BMSCs had CXCR4 expression. The number of apoptotic cells was significantly reduced in SDF-1 PC group as compared with the control group, and 100 ng/mL SDF-1 PC group had the lowest level of apoptosis. It was concluded that SDF-1 preconditioning suppresses the apoptosis of BMSCs treated with hypoxia plus serum deprivation.

This experiment was done to compare the effects of antegrade and retrograde cold cardioplegic solutions on myoeardium in the presence of coronary obstruction. Twelve mongrel dogs were anesthetized with intravenous pentobarbital, and immediately after the left anterior descending of coronary artery (LAD) was tied off, all subjects were randomly allocated to receiving antegrade cardioplegic solution (4 C) through arotic root at initial dose of 20ml?kg~(-1) and supplemental dose of 10ml?kg~(-1) with perfusion pressure being 10.7kPa every 20 minutes (group n=6), or antegrade cardioplegic solution in the same way as mentioned above at initial dose of 10ml?kg~(-1) and retrograde cardioplegic solution at initial dose 10ml?kg~(-1) and supplemental dose of 10ml?kg~(-1) with perfusion pressure being 5.3kPa every 20 minutes (group Ⅱ, n=6), respectively. The occlusion of LAD lasted 60 minutes. As compared with the values of group Ⅰ, in group Ⅱ, there was a lower hypothermia in the myocardial re gion supplied by LAD during ischemia (P

Objective: To observe the effect of on modified St.Thomas solution with mitochondrial ATP-sensitive potassium channel opener diazoxide on guinea pig papillary muscles protection after myocardial hypoxia. Methods: Twenty-four guinea pigs were randomly divided into three groups. In control group, cardioplegia was routine St.Thomas solution. In treatment group, cardioplegia was used modified St.Thomas solution. In blocker group, the muscle was treated with the specific potassium channel blocker glibenchamide 15 minutes before arrest used diazoxide cardioplegia. Myocardial electrophysical before and after cardioplegic arrest in guinea pig papillary muscles were studied. Results: 1, Time of recovery was shortened significantly in treatment group (P

Objective To investigate the effects of preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) on the levels of apoptosis of bone marrow stromal cells (BMSC) treated with hypoxia plus serum deprivation, and observe the therapeutic efficacy of cellular transplant with BMSC preconditioned with SDF-1 in rats with acute myocardial infarction. Methods BMSC were cultured with the whole marrow-adherence way. RT-PCR and immunohistochemistry were used to determine the expression of CXCR4. BMSC were incubated in medium for 24 h with 10 and 100 μg/L SDF-1 respectively, then treated with hypoxia plus serum deprivation for 6 h. The levels of apoptosis were detected by flow cytometry and TUNEL method. Acute myocardial infarction (AMI) model was established in SD rats, and BMSC preconditioned or non-preconditioned with SDF-1 were transplanted into border zone around infarct area, then heart function was measured after two weeks by ultrasonography. Results BMSC exhibited the CXCR4 expression. The number of apoptotic cells was significantly reduced in SDF-1 PC group than in control group (P<0.05), and 100μg/L SDF-1 PC group had the lowest level of apoptosis. AMI model was established successfully. Two weeks after BMSC transplant, significant improvement in cardiac function was observed in 100 μg/L SDF-1 PC group as compared with the non-PC group (P<0.05). Conclusions PC with the chemokine SDF-1 suppresses the apoptosis of BMSC treated with hypoxia plus serum deprivation. SDF-1 PC is a novel approach for enhancing therapeutic efficacy of cellular transplant in rats with AML

Objective To study the impact of NF-kappaB activation on TNF-a and IL-1β expression in myocardial ischemia/reperfusion(I/R) injury.Methods Sixty-five Sprague-Dawley rats were randomly divided into three groups:sham,n=5;I/R:30 min of myocardial ischemia followed by 0,15,30,60,120.240 min of reperfusion,n=5 per subgroup;I/R+PDTC:PDTC(15 mg/kg)was given before ischemia,and the time points were the same as those in I/R group.TNF-a and IL-1β mRNA expression was detected by RT-PCR,activity of NF-KB was measured by electrophoretic mobility shift assay (EMSA),and MDA level in myocardium was assayed by TBA method.Results The expression of TNF-a and IL-1β was increased before reperfusion,reached their peak at the time point of reperfusion 30.60 min respectively.and remained high level at the 2nd h after reperfusion.NF-KB was activated 15 min after reperfusion,reached its peak at the first h after reperfusion.In I/R+PDTC group,NF-κB activation was blocked by PDTC.As compared with I/R group,the expression levels of TNF-a and IL-1β were decreased to varying degrees at each time point.and the content of MDA was also reduced in I/R+PDTC group.Conclusion NF-KB activation could play a pivotabrole in the expression of cytokine.Inhibition of NF-κB signal pathway might be a potential therapeutic strategy in reperfusion injury.

In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups: the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 min, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group. MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced (P<0.05). And the cell ultrastructure was obviously improved. But the activity of SOD had no change (P>0.05). It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.
Apoptosis ; In Situ Nick-End Labeling ; Malondialdehyde/pharmacology ; Myocardium/*pathology ; Myocytes, Cardiac/cytology ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Pyruvates/*pharmacology ; Rats, Sprague-Dawley ; Reperfusion Injury ; Tissue Distribution ; bcl-2-Associated X Protein/*metabolism