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目的:探讨银杏二萜内酯葡胺注射液对线栓法致大鼠急性脑缺血再灌注损伤(MCAO)的保护作用,并探讨其可能的作用机制。方法:雄性SD大鼠96只,随机分为假手术组、模型组、尼莫地平(0.4 mg·kg-1)组、银杏二萜内酯葡胺注射液高、中、低(4.8,2.4,1.2 g·kg-1)剂量组。所有动物手术前2 d尾静脉注射给药(模型组及假手术组给予生理盐水)。除假手术组,其他动物通过右侧大脑中动脉线栓塞法(MCAO)制作局灶性脑缺血再灌注模型。缺血3 h后,所用动物再次尾静脉注射给药。采用脑组织TTC染色法观察梗死率;放免法测定血清中磷酸肌酸激酶脑型同工酶(CK-BB)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;免疫组化法测定脑组织中半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)表达。结果:与正常组比较,模型组大鼠脑梗死率显著增加,神经缺损症状严重;血清中SOD活性降低,MDA,CK-BB含量显著增加;脑组织中Caspase-3表达量显著升高。与模型组比较银杏二萜内酯葡胺注射液中剂量组能显著减少脑梗死率,改善脑神经功能缺损症状;提高SOD活性,减少血清中MDA,CK-BB含量,抑制脑组织中Caspase-3表达。结论:银杏二萜内酯葡胺注射液对大鼠局灶性脑缺血再灌注损伤具有保护作用,作用机制可能与其修复血脑屏障、降低血清CK-BB含量、抗自由基损伤及抑制Caspase-3表达有关。
Objective: To investigate the protective effect of ginkgo diterpene lactone meglumine injection on acute cerebral ischemia-reperfusion injury (MCAO) induced by thread plugging in rats and its possible mechanism. Methods: Ninety-six male Sprague-Dawley rats were randomly divided into sham operation group, model group and nimodipine (0.4 mg · kg -1) , 1.2 g · kg-1) dose group. All animals were given intravenous injection of tail vein 2 days before surgery (saline was given to the model group and the sham operation group). In addition to the sham operation group, other animals were subjected to a focal cerebral ischemia-reperfusion model by right middle cerebral artery occlusion (MCAO). After 3 h of ischemia, the animals used were given a tail vein injection again. TTC staining was used to observe the infarct rate. Serum CK, CK and SOD were detected by radioimmunoassay (RIA). Immunohistochemistry Method to measure the expression of caspase-3 in brain tissue. Results: Compared with the normal group, the cerebral infarction rate of the model group increased significantly, and the symptoms of the neurological deficit were serious. The activity of SOD in the serum was decreased and the contents of MDA and CK-BB were significantly increased. The expression of Caspase-3 in the brain tissue was significantly increased. Compared with the model group, the dose of ginkgo diterpene lactone meglumine injection could significantly reduce the infarction rate and improve the neurological deficit symptoms; increase the activity of SOD, decrease the content of MDA and CK-BB in serum, inhibit the expression of Caspase- 3 expression. CONCLUSION: Ginkgo biloba lactone meglumine injection has a protective effect on focal cerebral ischemia-reperfusion injury in rats. Its mechanism may be related to the repair of blood-brain barrier, serum CK-BB content, anti-free radical damage and inhibition of Caspase -3 expression.