丹参酮ⅡA对脑缺血再灌注大鼠脑损伤的保护作用及对能量代谢的影响

Protective effects of TanⅡA on brain injury induced by cerebral ischemia-reperfusion in rats and its effects on energy metabolism

目的观察丹参酮ⅡA(TanⅡA)对缺血再灌注大鼠脑损伤的保护作用及对能量代谢的影响。方法采用大鼠右侧大脑中动脉阻断(MCAO)局灶性脑缺血再灌注模型,缺血前给TanⅡA 8、16、32 mg·kg-1,灌胃7 d,末次给药1 h后线栓法制备大鼠MCAO短暂局灶性脑缺血模型,缺血2 h,再灌注22 h,分别用Longa’s法、TTC染色法、干燥失重法评价大鼠的神经功能状态、脑梗死面积及其脑水肿的程度;观察线粒体呼吸酶活性的变化;评价脑缺血再灌注损伤后脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)及脑ATP含量的变化。结果TanⅡA(16、32 mg·kg-1)可明显减少MCAO后脑梗死面积、脑水肿的程度及改善神经功能症状;同时TanⅡA(16、32 mg·kg-1)能明显抑制MCAO大鼠脑线粒体呼吸酶及SOD酶活性的降低,升高脑组织ATP含量,降低脑组织中MDA的含量。结论TanⅡA对脑缺血再灌注损伤有明显的保护作用,该作用的产生可能与其改善脑线粒体能量代谢、抗氧化作用有关。

AIM To investigate the protective effects of Tan Ⅱ A on brain injury after cerebral ischemia-reperfusion（I/R） and its effects on cerebral energy metabolism. METHODS Rats were pretreated with Tan Ⅱ A at the dose of 8,16,32 mg·kg^-1, ig for 7 d, respectively. And then subjected to cerebral I/R injury induced by a middle cerebral artery occlusion（MCAO）. After 2 h ischemia and 22 h reperfusion, the infarct volume, the extent of oedema and the neurological deficit were determined by the methods of 2,3,5-triphenyltetrazolium chloride（TTC）staining, dry-weightlessness and Longa＇ s score. The cerebral mitochondria were isolated for determination of the activities of mitochondrial repiratory enzymes, superoxide dismutase（SOD）, and the content of ATP and malonyldialdehyde（MDA） following cerebral I/R. RESULTS Tan Ⅱ A significantly reduced infarct volume, ameliorated the neurological deficit（ P 〈 0.05 or P 〈 0.01 ）. Tan Ⅱ A also inhibited the down-regulation of mitochondria respiratory enzymes and SOD, decreased MDA content and increased ATP level after cerebral I/R. CONCLUSION Tan Ⅱ A has protective effects on brain injury induced by cerebral I/R. The mechanisms may be related to its protective effects on mitochondria, improving cerebral energy metabolism and scavenging free radicals.