Effects Of Sulodexide On Focal Cerebral Ischemia-reperfusion Injure In Rats

ObjectiveIn the experiment, we established the model of focal cerebral ischemia-reperfusion in rats based on the model of middle cerebral artery occlusion (MCAO) to observe the effects on nervers function damages, the morphological changes of nerve cells and the expressions of tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP), after interfering with sulodexide. In order to investigate the neuroprotective effects and mechanisms of sulodexide on focal cerebral ischemia-reperfusion injure in rats.Methods72 Wistar rats were randomly divided into three groups, sham-operative group, model group and sulodexide group. The model of MCAO were made by the method of modified Zea Longa, blocked the left middle cerebral artery and reperfused after ischemia 2h. Sulodexide group were given intraperitoneal injection of Sulodexide 1mg/100g after ischemia-reperfusion 0h,12h,24h,48h, and the model group were given intraperitoneal injection of saline in the same dose. Sham-operative group only performed the neck incision, isolated the common carotid, internal carotid, external carotid artery, not blocked blood flow by tying into the line. At the appropriate point in time the head was disassociated and the brain was unloaded, the pathological changes in brain tissue were observed by using HE staining, the expressions of TNF-αand CRP was detected by immune-histochemical analysis.Results1. After middle cerebral artery was blocked for 2h, there were the varying severity of symptoms of neurological deficits, compared with the model group, in sulodexide group the neurological deficit score were significantly reduced at each time points after ischemia-reperfusion 12h (P<0.05).2. In the sham-operation group, the HE staining of brain tissue displayed:nerve cells arranged in neat, nuclear morphology was regular, into a round, located in the central of cell body, with a light color, nucleolus was clear, there were no edema, degeneration and necrosis. In model group, the HE staining of brain tissue displayed: nerve cells in ischemic core was unclear or missing, normal tissue structure of neurons and glial cells disappeared, showing that cell swelling, nuclear shrinkage, and even the formation of morphological changes of necrosis such as nuclear debris, and nuclear dissolution. In sulodexide group the changes above were lighted compared with model group.3. The expression of TNF-αwas detected by immune-histochemical staining analysis:in sham-operation group there were only a few positive cells; compared with the sham group the expression of TNF-αof the other two groups increased after ischemia-reperfusion 6h in the ischemic brain tissue,12h reached the peak,24h down,48h further decreased but still higher than the sham-operation group (P<0.01); compared with the model group, in sulodexide group the expression of TNF-αdecreased in ischemia-reperfusion 6h (P>0.05), after 12h at various time points the expression were significantly reduced (P<0.05).4. The expression of CRP was detected by immune-histochemical staining analysis:the sham group showed very few positive cells; the expression of CRP after ischemia and reperfusion 6h was significantly higher than the sham group,24h-48h sustained peak (P<0.01); compared with the model group, in sulodexide group the expression of CRP reduced in the ischemic 6h (P>0.05), after 12h at each time points the expression was significantly reduced (P<0.05). ConclusionsSulodexide could reduce the expression of TNF-αand CRP, lighten brain cell swelling and improve the symptoms of neurological deficit, sulodexide could protect the cerebrum after focal cerebral ischemia-reperfusion injure in rats.