| Background: Cerebral ischemia preconditioning can induce ischemic tolerance thus relieve the injury through reducing the quantity of dead parenchymal cell, deflating infarct volume,relieving neurological deficits etc. Human urinary kallikrein (hk1) can dilate the small arteries in ischemic region selectively; improve the blood supply of ischemic area. So that it has protective effect on the cell in ischemic region. Recently there are many studies on the expression of interleukine-6(IL-6)and neuroglobin (Ngb)in brain tissue and blood serum after cerebral ischemia, but there are few studies about the expression of them after the intervention of hk1. If cerebral ischemia preconditioning and hk1 have protective effect on the cells in ischemic region through influencing the expression of IL-6 and Ngb still not clear.Objective: To investigate the effects of ischemia preconditioning and intervention of hk1 on neurological function, infarct volume, expression of IL-6 and Ngb in brain tissue in rats after brain ischemia, and to investigate the brain protecting mechanism of ischemia preconditioning and hk1 and the interaction between them, in order to provide theoretical foundation for the clinical therapy of ischemic cerebrovascular disease.Methods:72 healthy male Sprague-Dawley (SD) rats (weighted 200~250g) were randomly divided into 3 groups: ischemia group (n=24), ischemia preconditioning group (n=24), and hk1 intervention group (n=24). Each group was further divided into 4 subgroups according to 12h, 1d, 2d, and 3d after re-ischemia (each subgroup=6) Ischemia preconditioning group: a focal-focal cerebral ischemic model was used, adopting the thread embolismmethod according to Koizumi. Exposing right common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA) of anaesthetized rats. Ligating ECA near head and cutting ECA away. Shearing a small mouth on the ECA near heart, and through it inserting a thread (a diameter 0.205mm carbon fishing line of high elasticity dripping candle for a round head at the end of the thread and dipping heparin before using) from ICA to anterior cerebral artery (ACA) to block MCA blood flow by 30 minutes, then pulling out the thread, ligating ECA nub, and sewing up the skin. After 24 hours, a thread was inserted to ACA in the right side again through CCA by 24 hours. Ischemia group: A thread was inserted to ACA in the right side directly through CCA by 24 hours. Intervention group: the rats are given the injection of hk1 through sublingual vein half hour after preconditioning. The following indexes in 3 groups were observed respectively: neurological function (according to Bederson method), pathological changes and expression of IL-6 and Ngb in hippocampal and cortical tissue of rats.Results1. At the same point of time after ischemia, the score of neurological impairment in preconditioning group was lower than that in ischemia group, the difference was significant (p<0.05). This score was lower in intervention group than that both in preconditioning group and ischemia group, the difference was significant (p<0.05).2.At the same point of time after ischemia, infarct volume in preconditioning group was smaller than that of ischemia group. The infarct volume in intervention group was also smaller than that both preconditioning group and ischemia group, the difference was significant (p<0.05).3. There was mass expression of IL-6 positive-cells in the hippocampus tissue after ischemia. They appeared 12 hours after ischemia and increased progressively, reached the peak 48 hours after ischemia and then gradually decreased, the difference between any two point of time in each group was significant (p<0.05). At the same point of time, the expression of IL-6 positive-cells was lower in preconditioning group than in ischemia group (p<0.05). The expression was also lower in intervention group than that both in preconditioning group and ischemia group.4. There was mass expression of Ngb positive-cells in the cortical areaafter ischemia. They appeared 12 hours after ischemia and increased progressively, reached the peak 24 hours after ischemia and then gradually decreased. The difference between any two point of time in one group was significant (p<0.05). At the same point of time, the expression of Ngb positive-cells was lower in preconditioning group than in ischemia group (p<0.05). The expression was also lower in intervention group than that in ischemia group (p<0.05).Conclusion1. Cerebral ischemia preconditioning can protect the neuron against the injury of the fatal brain ischemia followed, reduce the quantity of dead parenchyma cell, deflate infarct volume, relieve neuralgic impairment, reduce the expression of IL-6, increase the expression of Ngb, reduce the neuronal degeneration, necrosis and tissue edema.2. Prophylactic application of hk1 after temporal and non-fatal cerebral ischemia can reduce the quantity of dead parenchyma cell, deflate infarct volume,relieve organ functional impairment and reduce hippocampus tissue expression of IL-6, but have little effect on cortical tissue expression of Ngb.
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