â… .Effects Of Sodium Tanshinone â…¡A Sulfonate On Cardiac Hypertrophy And MAPK Signaling Pathway â…¡.Studies Of Postconditioning In Protection Of The Brain After Ischemia And Resucitation

Objective To construct cardiac hypertrophy model by partially binding thoracic aorta in rats. Methods Thirty male Sprague Dawley(SD) rats were divided into sham surgery (n=10) and operation (n=20) randomly. Operation methods: The suture was snugly tied around the 22-gauge needle and the aorta which was between the origin of the right innominate and left common carotid arteries. After ligation, the needle was quickly removed. Echocardiography,the external appearance and HE staining was performed 10 weeks after the surgery. Results After 10 weeks, the volume of heart in operated rats is increased than sham-operation groups. Compared with the sham-operated, M-mode demonstrated that the operated group's left ventricle (LV) cavity and the posterior wall thickness increased markedly and its fractional shortening decreased. Compared with sham-operation groups, the operated rats showed that the interventricular septum thickness (2.527+0.269 vs.1.943+0.1, P<0.01),and the posterior wall thickness (2.492+0.242 vs.1.902+0.076, P<0.01) increased; the fractional shortening diminished(49+7.681 vs.55.7+9.828,P>0.05); the cardiac hypertrophy index increased (3.196+0.11 vs.1.785+0.099,P<0.01); the changes of LV internal diastolic dimension (LVIDd),LV internal systolic dimension (LVIDs)and ejection fraction was not obvious. Conclusion Thoracic aorta constriction (TAC) induced rat cardiac hypertrophy will provide a reproducible model to study cardiac hypertrophy,myocardial dysfunction and myocardial remodeling.Objective To determinate the effects of Sodium Tanshinoneâ…¡A sulfonate (STS) on cardiomyocyte hypertrophy and explored the relative effects of STS on mitogen-activated protein kinase signal transduction system in rats with cardiomyocyte hypertrophy through constricting the thoracic aorta. Methods To make the models of cardiomyocyte hypertrophy in vivo, the thoracic aorta was partially tied between the right innominate and the left common carotid arteries. The rat randomly divided in 6 groups (n= 8/group) as follows:1) sham,2) transverse aortic constriction (TAC),3) TAC+Low-dose Tan (TAC+LT) (5mg/kg),4) TAC+ medium-dose Tan (TAC+MT) (10mg/kg),5)TAC+high-dose Tan (TAC+HT) (20mg/kg) and 6)TAC+Val (10mg/kg). After 8 week medication, Echocardiography was performed to measure the changes of hypertrophy and heart function, and heart samples were cut into transverse sections and stained with hematoxylin and eosin (H&E). The MAPKs protein expression in the cardiomyocytes was measured by western blot analysis. Results The heart weight index (HWI), left ventricular mass index (LVMI) and cross-sectional diameter of cardiomyocytes (CD), left ventricular posterior wall thickness (LVWT), interventricular septal thickness (IVS) were significantly increased than sham group as soon as 2 months post-TAC. And the relative parameters of STS groups and Val group were alleviated than the TAC group. Western blot analysis shows the p-ERK and p-p38 expression was significantly decreased in the TAC group compared with the sham group (p<0.01). The p-ERK expression was significantly decreased in the STS groups and Val group compared with the TAC group (p<0.05). The TAC+HT group, TAC+MT group and Val group had significantly higher p-p38 expression than the TAC group (p<0.05). Conclusion Tanshinoneâ…¡A could regulate the expression of protein in MAPK pathway to exert it inhibition of hypertrophy of cardiomyocyte.Objective:To study the effects of postconditioning on synaptic ultrastructure and synaptophysin expression in global cerebral ischemia reperfusion. Methods:To make the models of global cerebral ischemia in vivo,;the vertebral artery of rat were occluded and common their carotid arteries were transitorily cliped. The rats randomly divided in 3 groups (n= 8/group) as follows:1) control(C),2) ischemia reperfusion (I),3) ischemia+postconditioning (Post-con). Control group: beparated carotid artery and didnot blocked blood flow. Ischemia reperfusion group: bilateral carotid artery was occluded 10min then reperfusion. Ischemia+ postconditioning group:bilateral carotid artery was occluded 10min then executed postconditioning protocol (3 cycles of 15s reperfusion/15s clipping) before reperfusion. Fourty eight hours later the rat in 3 groups were killed and their brain tissues were harvested and made into slices, stained with immunohistochemical techniques, photographed under the transmission electron microscope and measured synaptophysin protein expression by western blot analysis. Results:â‘ it was observed in the ischemia+postconditioning (Post-con) group from electric mirror that there were a relatively large number of synaptic neuropil, and the damages of mitochondria and synaptic were minor, compared with the ischemia-reperfusion (Ischemic) group,â‘¡ischemia+postconditioning (Post-con) group compared with the ischemia-reperfusion (Ischemic) group:The immunoreactivity of synaptophysin in the hippocampus increased significantly; the immune products were larger particles, dense and deeply stained; cells arranged in regular and cell swellings were less.â‘¢Western blot analysis show the synaptophysin expression was significantly increased in the Post-con group compared with the ischemic group (P<0.05). Conclusion:Postconditioning reduced reperfusion injury in neurons, regulated neuronal plasticity and promoted the recovery of nerve function.Although current cardiopulmonary resuscitation (CPR) performance can increase the rates of restoration of spontaneous circulation (ROSC) and survival to hospital admission, the discharge rates of patients remain disappointing. The high mortality rate is attributed to post-cardiac arrest brain injury. The discovery of the postconditioning phenomenon opens a door to endogenous neuroprotection. The protection mechanisms of postconditioning include attenuating mitochondrial calcium overload and reducing oxidative stress, recruiting the reperfusion injury salvage kinase (RISK) pathway, and preventing from the mitochondrial permeability transition pore (mPTP) opening at the time of reperfusion. An advantage of postconditioning lies in the potentially clinical application in the unexpected ischemic situation. Prior laboratory researches indicate that postconditioning may lessen the reperfusion/ischemia-induced injury in unexpected coronary occlusion, acute myocardial infarction and stroke. Because cardiac arrest, stroke and acute myocardial infarction have a similar pathophysiological process, we hypothesize that postconditioning could be used in the clinical practice of CPR to treat patients with post-cardiac arrest brain injury. We propose a novel protocol of 'Postconditioning cardiocerebral resuscitation (Post-CCR)'. The Post-CCR includes applying three cycles of 18 seconds chest compression and 10 seconds interruption for ventilation first, and then executing chest compression only CPR until the patients return spontaneous circulation. Post-CCR can not only provide vital blood flow to the heart and brain but also activate endogenous protective mechanism to lessen post-cardiac arrest brain injury. We consider that it would become a feasible, safe and efficient cerebralprotective intervention in the prevention and alleviation of post-cardiac arrest brain injury, which would also improve the outcome after cardiac arrest.