| Objective:To explore the protective effects and possible mechanisms of EPCr on acute cerebral ischemia injury and MODS which is caused by cerebral ischemia reperfusion injury.Methods:1.Adult male SD rats, were randomly divided into sham operation group, model group, PCr0.5g·kg-1(PCr0.5) group, PCr1.0 g·kg-1 (PCr1.0) group and Nimodipine (Nim) control group. The model of focal brain ischemic reperfusion injury in rats was established by instraluminal thread method. Behavioral scores were evaluated at 4, 24h after reperfusion; brain infarction volume were determined by TTC staining; ECG changes were recorded during ischemic reperfusion periods in rats; the pathological changes of brain and lung tissue were observed by HE staining; CD14 positive expression in brain and lung tissue were detected by immunohistochemistry (IHC).2. Male Kunming mice, were randomly divided into 5 groups: sham, model, PCr0.5, PCr1.0 and Nim control. The model of global cerebral ischemia reperfusion injury in mice was made by repeated ligation-reperfusion bilateral common carotid arteries method. Brain water content was determined by Wet and dry weight ; CD14 protein expression in brain and lung tissue was detected by western blot Analysis .Results:1. The influence of EPCr on MCAO/RF injury and CMODS in rats. Compared with model(8.60±1.00, 8.30±1.10), the behavioral scores of PCr0.5 (5.80±1.70, 5.00±1.30), PCr1.0 (5.60±1.60, 4.70±1.50) at 4h, 24h/RF markedly decreased(P<0.05). Compared with model[(27.00±7.70)%], the cerebral infarction volume of PCr0.5[(6.00±3.40)%], PCr1.0[(5.50±3.40)%] significantly decreased (P<0.05). During ischemic reperfusion periods, ECG showed a markedly high and widen QRS wave, J point elevation, and had a significant cutting-edge twist at 24h/RF, PCr0.5, PCr1.0 significantly improved these changes [especially J point elevation (0.328±0.089)vs(0.265±0.049, 0.227±0.033), (P<0.05)]. Meanwhile, HE staining results showed brain and lung slices had significant pathological changes (edema, bleeding, inflammatory cell infiltration, etal.) after cerebral ischemia reperfusion injury, PCr0.5, PCr1.0 could improved these injury. The result of CD14 positive expression in brain and lung tissue with model[(39.70±9.25)%, (53.15±10.32) %] showed markedly increased, compared with model, CD14 positive expression in PCr0.5[(23.50±7.44)%, (36.78±7.25)%], PCr1.0[(19.60±6.32)%, (32.56±4.67)%] significantly decreased (P<0.05).2. The influence of EPCr on GBI /RF injury and CMODS in miceCompared with model [(82.28±1.85)%], the contents of brain water with PCr0.5[(79.43±0.80)%], PCr1.0[(79.08±0.65)%] significantly decreased(P<0.05). Compared with sham(0.48±0.13, 0.58±0.18), CD14 protein expression in brain and lung tissue with model(1.17±0.31, 1.62±0.25) showed markedly increased; compared with model, PCr0.5 (0.76±0.16, 1.20±0.24), PCr1.0(0.71±0.17,0.97±0.19) significantly decreased(P<0.05).Conclusion:1. In the experiments, instraluminal thread method and repeated ligation -reperfusion bilateral common carotid arteries method were used to establish the model of cerebral ischemia-reperfusion injury, this two models not only caused brain structure and function injury, but also caused other tissues or organs away from brain, and this results consisted with the pathological process of cerebral ischemia in clinical.2. EPCr could significantly reduce the structure and function injury of brain tissue in animals, which caused by global and focal cerebral ischemia reperfusion injury.3. EPCr can significantly reduce the secondary structure and function injury of heart and lung caused by brain damage.4. Perhaps, there existed a relationship between the protective effects of EPCr on CMODS and reduced CD14 expression in body.5. The results in this experiments provide exact experimental evidences for the application of EPCr on cerebral ischemic injury in clinical. |
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