| Objective:To observe the expression of VEGF, NOS and NOS on focal cerebralischemia-reperfusion injury in SD rats; to observe the influence of the expression ofVEGF, NOS and NOS on prophylactic use atorvastatin on focal cerebralischemia-reperfusion injury in SD rats; to disscuss whether with atorvastatin can relievethe injury of endothelial function on focal cerebral ischemia-reperfusion and possiblemechanism.Methods:90healthy male SD rats, according to the principle of randomly dividedinto three groups(n=30): sham-operated group, control group and atorvastatin calciumpretreatment group (atorvastatin group to abbreviate), thirty rats in each group. Eachgroup was divided into5subgroups according to reperfusion2h(n=6),6h(n=6),24h(n=6),48h(n=6),72h(n=6) after ischemia for2hours. Atorvastatin regimencontinued rats, preoperative14days to atorvastatin regimen continued (10mg/kg/d) lineirrigation treatment stomach,1time/day; sham-operated group and control group are inpreoperative14days in the stomach with volume and0.9%sodium chloride solution,1time/day.Using the improved Longa-Zea method to establish ischemia-reperfusion modelin right cerebral middle artery of SD rat (each group was made ischemia-reperfusionmodel except the sham-operated group). Evaluate the neurological impairment score byreferring to Zea-Longa’s standards of five grades; all removed brains was stainedrespectively with2%Tripheny Tetrazalium Chloride(TTC); Judging the ischemiclocation, measuring the infarction pathomorphology through Hematoxylin-eosin(HE);observing the expression of VEGF with immunohistochemical technique. Use chemicalcolorimetric to detect the content of NO and the activity of NOS. To compare:(1) The expression of VEGF, NO and NOS at the same reperfusion time betweenatorvastatin group and control group;(2) The expression of VEGF, NO and NOS at the same reperfusion time betweencontrol group and sham-operated group;(3) Dynamic changes of neurologic impairment score,cerebral infarction volume,VEGF, NO, NOS at every point of time in control group;(4) Dynamic changes of neurologic impairment score,cerebral infarction volume,VEGF, NO, NOS at every point of time in atorvastatin group.Results:1. Changes in neurologic impairment score: The neurological impairment scorein control group was higher than that in the sham-operated group at every subgroup andthe result has remarkable difference(P<0.01); Zea-Longa evaluation have no differencebetween the atorvastatin group and the control group except in the group of24h、48hand72h reperfusion following2h cerebral ischemia(P<0.05).2. Changes in cerebral infarction volume: Sham-operated group have noinfarction area; the infarction volume appear at2h cerebral ischemia-reperfusion andincreased gradually after reperfusion in the control group and the atorvastatin group;compare with the difference between control group group and Sham-operated group,the difference was remarkable(P<0.01); the infarction volume showed no differencebetween the atorvastatin group and the control group except in the group of24h、48hand72h reperfusion following2h cerebral ischemia(P<0.05).3. HE dyed observation: Sham-operated group have no infarction areas andevident pathological change; the number of neuron at ischemic area decreased,nervecells shrank and degenerated, apparent edema between tissues and vacuolization incontrol group; compared with control group, the number of neuron which appareddegeneration and necrosis decreased, vacuolization and inter-tissue edema becamerelieved in atorvastatin group.4. The expression of VEGF: Sham-operated group have no VEGF cells;incontrol group and atorvastatin group, a few of VEGF positive cells can be seen at2hcerebral ischemia, it increased since2h after reperfusion and reached the peak at24hafter reperfusion, then decreased gradually, compared every adicant reperfusion timepoint in control group and atorvastatin group, the difference was remarkable (P<0.01);the number of VEGF positive cells in atorvastatin group, were higher than that in control group, the difference was remarkable at reperfusion2h、6h(P<0.05) and24h、48h、72h(P<0.01).5. Content of NO: Sham-operated group have no difference; compared everyadicant reperfusion time point between control group and Sham-operated group, thecontent of NO increased obviously except2h after reperfusion in control group, thedifference was remarkable at reperfusion6h (P<0.05) and24h、48h、72h(P<0.01); incontrol group and atorvastatin group, the content of NO increased since6h afterreperfusion and reached the peak at24h after reperfusion,then decreased gradually,compared with control group, the content of NO reduced at every adicant reperfusiontime point, the difference was remarkable at reperfusion6h、24h、48h and72h(P<0.05).6. Activity of NOS: Sham-operated group have no difference; compared everyadicant reperfusion time point between control group and Sham-operated group, theactivity of NOS increased obviously since6h after reperfusion in control group, thedifference was remarkable (P<0.01); in control group and atorvastatin group, theactivity of NOS enhanced since6h after reperfusion and reached the peak at24h afterreperfusion, then weakened gradually, compared with control group, the activity ofNOS weakened at every adicant reperfusion time point, the difference was remarkableat reperfusion6h、24h、48h and72h(P<0.05).Conclusions:1. The expression of VEGF、NO、NOS can be increased in the process of cerebralischemia-reperfusion injury in SD rats.2. Prophylactic use atorvastatin could increase the expression of VEGF, reducedthe content of NO and the activity of NOS.3. Prophylactic use atorvastatin could decrease focal cerebral ischemia-reperfusion injury, relive the neurological functional defect, reduce infracted volume,relieve the neuronal degeneration, necrosis and tissue edema, the neuroprotectivemechanism of atorvastatin may be increase the expression of VEGF, reduced thecontent of NO and the activity of NOS on focal cerebral ischemia-reperfusion injury. |
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