双苯氟嗪对脑缺血再灌注损伤后脑组织及血清中NO、NO S、iNO S的影响

目的研究双苯氟嗪(D ipfluzine,D ip)对大鼠脑缺血再灌注损伤模型的脑组织及血清中一氧化氮(NO)含量、一氧化氮合酶(NOS)及诱导型一氧化氮合酶(iNOS)活性的影响。方法选用♂SD大鼠,随机分为7组:假手术组、缺血再灌注组、溶剂对照组、D ip(0.5、1.0、和2.0 mg.kg-1)治疗组、氟桂利嗪(F lunarizine,F lu)1.0 mg.kg-1阳性对照组。采用改良的Pu lsinelli四动脉结扎法制备大鼠全脑缺血15m in再灌注24 h模型,并于再灌注开始时尾静脉注射给药。分别观察各组大鼠脑海马CA1区神经元形态学变化以及脑组织和血清中NO含量和NOS、iNOS活性的变化。结果形态学观察可见:假手术组细胞排列整齐、紧密,胞核大而圆,透明,核仁清晰可见,缺血再灌组和溶剂对照组细胞排列松散,胞体缩小,核不规则。双苯氟嗪和氟桂利嗪均可明显改善这种损伤性改变。与假手术组相比,缺血再灌注组和溶剂对照组脑组织和血清中NO含量和NOS、iNOS活性明显升高;与溶剂对照组相比,D ip 1.0 mg.kg-1组、D ip 2.0 mg.kg-1组及F lu组脑组织和血清中NO的含量、iNOS活力、以及脑组织中NOS活力均明显降低。结论双苯氟嗪可降低NOS、iNOS活性,减少NO含量,减轻神经元损伤程度,具有脑保护作用。

Effects of dipfluzine on the contents of NO and the activitives of NOS and iNOS in the brain tissue and serum of rats after global cerebral ischemia-reperfusion injury

Aim To observe the effects of Dipfluzine on the contents of NO and the activities of NOS and iNOS in the brain tissue and serum of rats after global cerebral ischemia-reperfusion injury.Methods Rats were randomly divided into seven groups:sham operation group,ischemia-reperfusion group,solvent group,Dip(0.5,1.0,2.0 mg·kg~(-1)) group,and Flu 1.0 mg·kg~(1) group.Transient global ischemia model(15 min ischemia followed by 24 h reperfusion) was set up using Pusinellis four-vessel occlusion method.Drugs were given by caudal vein injection when starting reperfusion.The morphological changes of neuron in hippocampal CA_1 sector were examined under microscope.And the contents of NO and the activities of NOS and iNOS in each group were measured respectively.Results In the sham operation group,the cells ranged regularly in hippocampal CA_1 sector,the nuclei were big,round and pellucid and easily observable.In the I-R 24 h and solvent groups,the cells ranged disorderly,with shrank cell bodies,and irreglar nuclei.Dip and Flu obviously improved the injuries mentioned above in different degrees.Compared with the sham operation group,the contents of NO and the activities of NOS and iNOS in the brain tissue and serum were greatly increased in the ischemia-reperfusion and solvent groups.After the treatment of Dip(1.0,2.0 mg·kg~(-1)) and Flu,the contents of NO and activity of iNOS in the brain tissue and serum and the activity of NOS in the brain tissues were decreased.Conclusion Dipfluzine may play a protective role against the ischemia-reperfusion injury by decreasing the activities of NOS and iNOS and the content of NO.