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补阳还五汤有效部位对动物全脑缺血损伤的保护作用及抗氧化与凋亡机制 被引量:22

Effective fraction from Buyang Huanwu Decoction exerts neuroprotective effect on global brain ischemia injury in rodent models via inhibiting lipid peroxidation and apoptosis
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摘要 目的:研究补阳还五汤有效部位对动物全脑缺血损伤的保护作用及可能机制。方法:采用小鼠断头法致全脑缺血缺氧模型,测定小鼠断头后呼吸持续时间,夹闭气管测小鼠心电持续时间;采用改良的四血管阻断法(Four-vessel occlusion,4-VO)建立大鼠全脑缺血再灌注损伤模型,记录大鼠脑电图(EEG)波幅的变化,测定脑组织含水量、血清乳酸脱氢酶(LDH)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,HE染色观察脑组织病理形态学改变,DNA原位末端缺口标记法(TUNEL)检测脑组织细胞调亡。结果:补阳还五汤有效部位(250、125、62.5mg/kg)显著延长小鼠断头后张口喘气时间;补阳还五汤有效部位(250、125mg/kg)显著延长小鼠夹闭气管心电持续时间;在大鼠四动脉结扎致全脑缺血再灌注模型上,补阳还五汤有效部位(200mg/kg)使大鼠脑电图恢复迅速,再灌注5min和60min后,脑电图幅度与模型组比较有显著性差异;补阳还五汤有效部位(200、100mg/kg)明显降低大鼠全脑缺血再灌注损伤后脑组织含水量;补阳还五汤有效部位(200、100、50mg/kg)显著抑制大鼠血清乳酸脱氢酶(LDH)活性并升高谷胱甘肽过氧化物酶(GSH-Px)活力,200mg/kg剂量组显著降低大鼠血清丙二醛(MDA)的含量;病理组织学检查显示,补阳还五汤有效部位(200、100、50mg/kg)明显改善全脑缺血再灌注损伤大鼠的神经细胞损伤,减少组织坏死;原位末端缺口标记(TUNEL)法检测大鼠脑组织细胞凋亡发现,补阳还五汤有效部位(200、100、50mg/kg)显著抑制脑组织细胞凋亡。结论:补阳还五汤有效部位对小鼠、大鼠全脑缺血损伤有显著的保护作用,其作用机制可能与抗自由基损伤、抑制细胞凋亡有关。 Objective: To study the neuroprotective effect and potential mechanisms of effective fraction from Buyang Huanwu Decoction( EFBHD)against global cerebral ischemia injury in rodent models. Methods: The acute cerebral anoxia mice induced by decapitation was used to evaluate the anti-hypoxic effect of drugs. The duration of electrocardiograph( ECG) after clamping trachea was observed in mice. Global cerebral ischemia reperfusion injury was caused by four vessel occlusion( bilateral vertebral arteries and bilateral carotid arteries,4-VO) in rats. The electroencephalographic( EEG) changes were recorded. The content of malondialdehyde( MDA),the activity of lactate dehydrogenase( LDH) and Glutathione peroxidase( GSH-PX) in plasma,and the water content of brain were measured. The cellular morphologic changes were observed by HE staining method. Neuronal cell apoptosis of cerebral tissues was detected with TUNEL method. Results: EFBHD( 250,125,62. 5mg/kg) significantly prolonged mice gasping time after decapitation. EFBHD( 250,125mg/kg) markedly prolonged the ECG time after lamping trachea on the cerebral anoxia model induced by clamping trachea in mice. Compared with the model group,EFBHD( 200 mg/kg) improved the EEG change of rats by 4-VO. EFBHD( 200 mg/kg) markedly decreased the MDA content in serum,and EFBHD( 200,100,50 mg/kg) decreased the LDH activity while the GSH-Px activity increased in serum. EFBHD( 200,100 mg/kg) significantly reduced the water content of brain induced by global brain ischemia-reperfusion injury in rats. Histopathology examination showed that sham group had no infarction areas and evident pathological change,and in model group,the number of neurons at ischemic area decreased,nerve cell was damaged by 4-VO in rats. And EFBHD inhibited the apoptosis of nerve cells of cerebral tissues by 4-VO in rats. Conclusions: These results indicated that the effective fraction from Buyang Huanwu Decoction could effectively improve cerebral function a
出处 《中药药理与临床》 CSCD 北大核心 2017年第4期2-7,共6页 Pharmacology and Clinics of Chinese Materia Medica
基金 安徽省高等学校省级自然科学研究项目(重点项目) 项目编号:(KJ2014A260)
关键词 补阳还五汤有效部位 脑缺血再灌注 脑电图 抗氧化 细胞凋亡 Effective fraction from Buyang Huanwu Decoction(补阳还五汤有效部位) cerebral ischemia injury electroencephalographic antioxidant apoptosis
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