| Part I:The neuroprotection induced by parecoxib treatment against cerebral ischemia/reperfusion injuryObjective:To investigate the neuroprotective effect of4mg/kg or20mg/kg parecoxib treatment against cerebral ischemia/reperfusion injury in rats. Methods:Adult male Sprague-Dawley rats (300～350g) were randomly assigned into four groups:the sham group (Sham), ischemia/reperfusion group (I/R), ischemia/reperfusion+4mg/kg parecoxib group (Parecoxibl), ischemia/reperfusion+20mg/kg parecoxib group (Parecoxib2). The left middle cerebral artery was permanently occluded by bipolar electrical coagulation and both commom carotid arteries were occluded with miniature clips for60min. The Parecoxib groups received parecoxib4mg/kg or20mg/kg intravenously15min before ischemia and again at12h after ischemia, and the Sham and I/R groups received normal saline in the same way. Physiological variables (mean arterial blood pressure, heart rate, temperature, and arterial blood gases) were measured at5min after induction of anesthesia,15min after ischemia, and15min after reperfusion. The neurologic deficit scores (NDSs) were evaluated at Id,3d and7d after reperfusion. Infarct volume was assessed with2,3,5-triphenyltetra-zolium chloride (TTC) staining at3d after reperfusion. Results:No difference was found in rectal temperature, mean arterial blood pressure, arterial pH, PaCO2and PaO2in the four groups (P>0.05). Compared with the I/R group, the Parecoxib1and Parecoxib2groups improved the neurological functions at1d,3d and7d after reperfusion (P<0.05). Animals in the Parecoxibl and Parecoxib2developed smaller brain infarct volumes than the I/R group at3d after reperfusion (P<0.05). But no difference was found in NDSs and infarct volumes between the Parecoxib1and Parecoxib2groups (P>0.05). Conclusions:Parecoxib treatment could induce the neuroprotection against cerebral ischemia/reperfusion injury, but the protective effect was not dose-dependent in this model. Part II:The neuroprotection induced by parecoxib treatment via anti-inflammation pathway against cerebral ischemia/reperfusion injuryObjective:To investigate the neuroprotective effect of parecoxib via anti-inflammation pathway against cerebral ischemia/reperfusion injury in rats. Methods:Adult male Sprague-Dawley rats (300～350g) were randomly assigned into three groups:the sham group (Sham), ischemia/reperfusion group (I/R), parecoxib group (Parecoxib). The left middle cerebral artery was permanently occluded by bipolar electrical coagulation and both commom carotid arteries were occluded with miniature clips for60min. The Parecoxib group received parecoxib4mg/kg intravenously15min before ischemia via vena dorsalis penis and again at12h after ischemia. The NDSs, Hematoxylin and eosin staining, Nissl staining, and expression of Tumor necrosis factor-a (TNF-a) and High mobility group box1protein (HMGB1) were evaluated at1d,3d and7d after reperfusion. Infarct volume was assessed with TTC staining at3d after reperfusion. Results:Compared with the I/R group, parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased TNF-a and HMGB1expressin (P<0.05). Conclusions:Treatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators. Part III:The neuroprotection induced by parecoxib treatment via the PKA/CREB pathway against cerebral ischemia/reperfusion injuryObjective:To investigate the neuroprotective effect of parecoxib via PKA/CREB pathway against cerebral ischemia/reperfusion injury. Methods:Adult male Sprague-Dawley rats (300～350g) were randomly assigned into five groups:Adult male Sprague-Dawley rats (300～350g) were randomly assigned into three groups:the sham group (Sham), ischemia/reperfusion group (I/R), parecoxib group (Parecoxib), ischemia/reperfusion+H-89group (H-89), parecoxib+H-89group (Parecoxib+H-89). The left middle cerebral artery was permanently occluded by bipolar electrical coagulation and both commom carotid arteries were occluded with miniature clips for60min. The Parecoxib groups received parecoxib4mg/kg intravenously15min before ischemia via vena dorsalis penis and again at12h after ischemia. The NDSs, and expression of CREB and BDNF were evaluated at Id,3d and7d after reperfusion. Infarct volume was assessed with TTC staining at3d after reperfusion. Results:Compared with the I/R group, parecoxib administration significantly improved NDSs, reduced infarct volume, and increased CREB and BDNF expressin (P<0.05). The effect was abolished by H-89(P<0.05). Conclusions:Treatment with intravenous parecoxib was neuroprotective. The neuroprotection of parecoxib may be mediated by PKA/CREB pathway. Part IV:Effect of parecoxib treatment on autophagy against cerebral ischemia/reperfusion injuryObjective:To investigate the neuroprotective effect of parecoxib via autophagy pathway against cerebral ischemia/reperfusion injury in rats. Methods:Adult male Sprague-Dawley rats (300～350g) were randomly assigned into four groups:the sham group (Sham), ischemia/reperfusion group (I/R), parecoxib group (Parecoxib), ischemia/reperfusion+3-MA group (3-MA). The left middle cerebral artery was permanently occluded by bipolar electrical coagulation and both commom carotid arteries were occluded with miniature clips for60min. The Parecoxib group received parecoxib4mg/kg intravenously15min before ischemia via vena dorsalis penis and again at12h after ischemia. The NDSs, Nissl staining, and Beclinl expression were evaluated at Id,3d and7d after reperfusion. Infarct volume was assessed with TTC staining at3d after reperfusion. Results:Compared with the I/R group, parecoxib and3-MA administration significantly improved NDSs, reduced infarct volume, increased alive neurons and decreased Beclinl expression (P<0.05). Conclusions:Treatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of autophagy and the inhibition of Beclinl expression. |
PDF Full Text Request