银杏叶制剂对正常脑温脑缺血大鼠的脑保护作用(英文)

Cerebral protective reaction of ginkgo biloba extract in normothermia cerebral ischemic rat

背景:在银杏叶提取物治疗脑缺血的实验研究中,由于使用全身麻醉药物,有可能诱导脑温改变,影响实验结果准确性。目的:研究常温状态下,国产银杏叶提取物对脑缺血再灌注组织抗氧化酶、脂质过氧化物及脑缺血组织含水量的影响。设计:随机对照的实验研究。地点和材料:实验在华中科技大学同济医学院完成。取24只Wistar大鼠,体质量为250～300g,将实验大鼠随机分为假手术组(n=8)、脑缺血对照组(n=8)、脑缺血银杏叶提取物治疗组(n=8),对照组及治疗组参考Nagasawa方法,制备正常脑温大鼠左侧大脑中动脉缺血2h再灌注2h动物模型,进行对照研究。干预:实验大鼠的脑温用颞肌温度反映,将测温探头包埋入大鼠左侧颞肌深部贴近骨外膜,用半导体氧化物温度传感器连续监测。用60W白炽灯头部加温和自动双控颅脑降温仪调节脑温,使脑温维持在常温(36.5～37℃)水平。按设计方案制备正常脑温大鼠脑缺血再灌注损伤模型,脑缺血银杏叶提取物治疗组大鼠在手术前12,8,4h和脑缺血及再灌注即刻,分别腹腔内注射银杏叶提取物注射液,每次3mL,共5次。脑缺血对照组及假手术组大鼠腹腔内注射相同次数和剂量的生理盐水。主要观察指标:脑缺血组织超氧化物歧化酶、谷胱甘肽过氧化物酶、还原型谷胱甘肽、丙二醛含量及脑缺血组织含水量。

BACKGROUND:In the researches of Ginkgo Biloba Extract(GBE) in the treatment of cerebra ischemia,because of the application of generally anaesthesia medication that may induce the alteration of cerebral temperature,the accuracy of the results may be affected. OBJECTIVE:To investigate the impact of domestic GBE on antioxidase and lipid peroxide of cerebral ischemic reperfusion tissue as well as the water content of ischemic brain tissue under normothermia. DESIGN:A randomised controlled trial. SETTING and MATERIALS:Study was conducted in the Tongji Medical University of Huazhong Science and Technology University.A total of 24 Wistar rats with a mass from 250 g to 300 g were randomly allocated into sham operation group(n=8),cerebral ischemia control group(n=8) and cerebral ischemia GBE treatment group(n=8).The animal model of normothermia rat with left middle cerebral artery ischemia for 2 hours and reperfusion for 2 hours was prepared with the reference of Nagasawa method in the animals of control group and treatment group for contrast study. INTERVENTIONS:The cerebral temperature of the rats was reflected by the temperature of the temporal muscle.The temperature measuring probe was embedded into the deep part of the left temporal muscle closed to osseous ectoblast.The temperature was continuously monitored by semiconductor oxide temperature sensor.The temperature of the head was heated with 60 W filament lamp and adjusted by automatic double controlling craniocerebral cooling instrument to maintain the cerebral temperature at normothermia level of 36.5 ℃-37 ℃.The normothermia cerebral ischemic reperfusion injury rat model was established according to the design.GBE injection was injected respectively into abdominal cavity in the rats of cerebral ischemia GBE treatment group at the following time point:12 hours,8 hours and 4 hours before operation,immediately after cerebral ischemia and immediately after reperfusion,with 3 mL each time and 5 times in total.Same times and dose of normal saline was injected into the abdominal cavity in the rats of both control group and sham operation groups. MAIN OUTCOME MEASURES:Superoxide dismutase(SOD),glutathione peroxidase(GSH Px),reduced glutathione(GSH),malondialdehyde(MDA) and water contents in the cerebral ischemic tissue. RESULTS:The levels of SOD,GSH Px and GSH in cerebral ischemia control group were(73.35±12.86) NU/mg,(167.37±54.34) μkat/g and(196.84±22.75) μg/g respectively,which significantly lower than that(96.02±16.83) NU/mg,(338.57±84.02) μkat/g and(337.51 ±34.89) μg/g of sham operation group(P< 0.01 or P< 0.05).The SOD,GSH Px and GSH levels of cerebral ischemia GBE treatment group were(87.24±15.03) NU/mg,(316.56±93.52) μkat/g and(263.16 ±28.54) μg/g,which significantly higher than that of cerebral ischemia control group(P< 0.01 or P< 0.05).The MDA level of cerebra ischemia control group was(308.34±26.81) nmol/g,which significantly higher than that(101.46±10.97) nmol/g of sham operation group(P< 0.01). The MDA level of cerebral ischemia GBE treatment group was(125.86 ±13.90) nmol/g,which was significantly lower than that of sham operation group(P< 0.01).The water content of cerebral ischemia control group was(80.45±0.44)%,which was significantly higher than that(78.20±0.25)%of sham operation group(P< 0.01).The water content of cerebral ischemia GBE treatment group was(79.63±0.46)%,which was significantly lower than that of cerebral ischemia control group(P< 0.05). CONCLUSION:Domestic GBE can inhibit the excessive production of free radicals and the lipid peroxidation during cerebral ischemia and reduce cerebral oedema and the destruction of blood brain barrier to protect cerebral ischemic tissues under cerebral normothermia.