大黄酚对小鼠脑缺血再灌注引起肝损伤的保护作用

神经药理学报 ›› 2014, Vol. 4 ›› Issue (4): 1-9.

• 研究论文 • 下一篇

大黄酚对小鼠脑缺血再灌注引起肝损伤的保护作用

赵薇, 李方江, 王树

1. 河北北方学院药学系，张家口，075000，中国
2. 河北北方学院第一附属医院心血管内科，张家口，075000，中国

出版日期:2014-08-26 发布日期:2015-01-20
通讯作者: 王树，男，副教授，硕士生导师；研究方向：心脑血管损伤研究；Tel: 86-313-4029318， E-mail:wangshu388@163.com
作者简介:赵薇，女，硕士研究生；研究方向：心脑血管损伤研究；E-mail:670734978@qq.com
基金资助:
河北省科技支撑计划项目(No.07276166), 河北北方学院自然科学研究项目(No. 2010022)

Protective Effects of Chrysophanol on Liver Injury Induced by Cerebral Ischemia-Reperfusion in Mice

ZHAO Wei, LI Fang-jiang, WANG Shu

1. Department of Pharmacy, Hebei North University, Zhangjiakou, 075000, Hebei, China
2. Department of Cardiovascular Medicine, The First Affiliated Hospital, Hebei North University, Zhangjiakou, 075000, Hebei, China

Online:2014-08-26 Published:2015-01-20
Contact: 王树，男，副教授，硕士生导师；研究方向：心脑血管损伤研究；Tel: 86-313-4029318， E-mail:wangshu388@163.com
About author:赵薇，女，硕士研究生；研究方向：心脑血管损伤研究；E-mail:670734978@qq.com
Supported by:
河北省科技支撑计划项目(No.07276166), 河北北方学院自然科学研究项目(No. 2010022)

摘要/Abstract

摘要： 目的：研究大黄酚（chrysophanol, Chry）对脑缺血再灌注引起肝损伤的保护作用及初步分子机制。方法：采用改良的Himori法建立小鼠脑缺血再灌注模型，随机将实验小鼠分为空白对照组、假手术组、模型组、大黄酚组(10.0, 1.0, 0.1 mg·kg-1)。采用生化方法检测小鼠血浆谷丙转氨酶（alanine aminotransferase, ALT）、谷草转氨酶（aspartate transaminase, AST）、超氧化物歧化酶（superoxide dismutase, SOD）、丙二醛（malondialdehyde, MDA）的变化；肝脏组织中SOD和MDA的变化；免疫组化法检测Caspase3的表达及原位杂交法测定caspase-3 mRNA的表达。结果：空白对照组和假手术组各项指标均无明显变化；模型组血清中ALT和AST含量增高，SOD活力减低，MDA含量增高，肝脏组织中SOD活力减低，MDA含量增高，Caspase-3及Caspase-3 mRNA表达明显增多；大黄酚组(10.0, 1.0, 0.1 mg·kg-1)血清中ALT和AST含量显著降低，SOD活力增高，MDA含量减低，肝脏组织中SOD活力增高，MDA含量减低，Caspase-3及caspase-3mRNA表达显著减少。结论：脑缺血再灌注可继发肝脏损伤，大黄酚可保护脑缺血再灌注引起的肝损伤，其机制可能是减少Caspase-3及caspase-3mRNA表达，抑制细胞凋亡，增强机体的抗氧化应激能力。

关键词: 大黄酚, 脑缺血再灌注, 肝损伤, Caspase-3, 氧化应激

Abstract: Objective: To research the protective effects of chrysophanol(Chry) on liver injury induced by cerebral ischemia-reperfusion in mice and its molecular preliminary mechanism. Methods: By improved Himori method, Cerebral ischemia-reperfusion injury model of mice was produced in conscious mice by temporarily obstructing bilateral common carotid arteries. The mice were randomly divided into six groups: control group, sham-operated group, model group, chrysophanol group (10.0, 1.0, 0.1mg·kg-1). The alanine aminotransferase(ALT), aspartate transaminase(AST), superoxide dismutase(SOD) and malondialdehyde(MDA) in the plasma and the SOD and MDA in the liver were measured with biochemical methods in mice. The expression of Caspase3 was determined by immunohistochemistry, and the expression of Caspase3 mRNA was detected using in situ hybridization assay. Results: There are no obvious pathological changes in various indicators between control group and sham-operated group. For mice of modle group, the concentration of ALT, AST, MDA increased and the activity of SOD decreaed in plasma; the concentration of MDA increased and the activity of SOD decreaed in liver; the expression of Caspase3 and Caspase3 mRNA strengthened in liver. For mice of chrysophanol group, chrysophanol(10.0, 1.0, 0.1 mg·kg-1) could decrease the concentration of ALT, AST, MDA and increase the activity of SOD in plasma; chrysophanol(10.0, 1.0, 0.1 mg·kg-1) could decrease the concentration of MDA and increase the activity of SOD in liver; and chrysophanol(10.0, 1.0, 0.1 mg·kg-1) could attenuate the expression of Caspase3 and Caspase3 mRNA in liver. Conclusions: Cerebral ischemia-reperfusion may cause liver damage secondarily. Chrysophanol showed the protective effects on injury liver in mice with cerebral-schemia reperfusion injury, perhaps the mechanism is involved in attenuating the expression of Caspase3 and Caspase3 mRNA, then inhibiting the cell apoptosis, enhancing the ability of the antioxidative stress.

Key words: chrysophanol, cerebral ischemia-reperfusion, liver injury, caspase-3, oxidative stress

中图分类号:

R965

赵薇, 李方江, 王树. 大黄酚对小鼠脑缺血再灌注引起肝损伤的保护作用[J]. 神经药理学报, 2014, 4(4): 1-9.

ZHAO Wei, LI Fang-jiang, WANG Shu. Protective Effects of Chrysophanol on Liver Injury Induced by Cerebral Ischemia-Reperfusion in Mice[J]. Acta Neuropharmacologica, 2014, 4(4): 1-9.

参考文献

[1]   李建生, 李建国, 赵君枚, 等. 川穹嗪和参麦注射液对老龄大鼠脑缺血再灌注多器官损伤的作用[J]. 中国中西医结合急救杂志, 2000, 7(5): 289-294.

[2]   Taizen Nakase, Takashi Yazamaki, Naoko Qura, et al. The impact of inflammation on the pathogenesis and prognosis of ischemic stroke[J]. J Neurol Sci, 2008, 271(2): 104.

[3]   Norio Himori, Hiroshi Watanabe, Akaike Nobuhide, et al. Cerebral ischemia model with conscious mice: involvement of NMDA receptor activation and derangement of learning and memory ability [J]. J Pharmacol Meth, 1990, 23(4): 311-327.

[4]   王树, 张力, 张丹参, 等. 大黄酚对脑缺血再灌注小鼠探索功能的影响[J]. 时珍国医国药, 2007, 18 (12): 3011-3013.

[5]   王树, 薛贵平, 张丹参, 等. 大黄酚对脑缺血再灌注小鼠学习记忆障碍及耐缺氧的影响[J]. 陕西医学杂志, 2008, 37(4): 402- 404.

[6]   王树, 张丹参, 张力, 等. 大黄酚对脑缺血再灌注小鼠记忆功能的保护作用[J]. 中国老年学杂志, 2009, 29 (15): 1934-1936.

[7]   王树, 张丹参, 薛贵平, 等. 大黄酚对脑缺血再灌注小鼠脑组织H2O2和CAT的影响[J]. 中药药理与临床, 2008, 24(4): 22-24.

[8]   李超, 张丹参, 赵晓倩, 等. 三种大黄酚制剂改善脑缺血/再灌注小鼠记忆功能的实验筛选研究[J]. 中国药理学通报, 2010, 26(12): 1607-1612.

[9]   张丹参, 张力, 薛贵平, 等. 大黄酚的抗衰老作用[J]. 中国医院药学杂志, 2005, 25(1): 15-17.

[10] 颜娟. 大黄酚脂质体对小鼠脑缺血再灌注损伤的神经保护作用及机制研究[D]. 石家庄: 河北医科大学, 2014.

[11] 范红斌, 邱丽颖, 李英. 脑缺血再灌注时肝脏损伤的形态学变化及阿司匹林的保护作用[J]. 中国老年学杂志, 2011, 7(31): 2513-2514.

[12] 宫伟红. 高脂血症合并急性脑缺血再灌注诱导大鼠肝损伤机制的研究[D]. 武汉: 武汉科技大学, 2012.

[13] Hiromi Shinagawa Aki, Motoki Fujita, Susumu Yamashita, et al. Elevation of jugular venous superoxide anion radical is associated with early inflammation, oxidativestress, and endothelial injury in forebrain ischemia-reperfusion rats [J]. Brain Res, 2009, 1292: 180–190.

[14] 牛文民, 刘智斌, 杨晓航, 等. 针刺保肝护脑对脑缺血再灌注肝损伤大鼠γ-谷氨酰半胱氨酸合成酶表达的影响[J]. 广州中医药大学学报, 2012, 29(5): 537-541.

[15] Mabel M Cortes-Wanstreet, Erich Giedzinski, Charles L Limoli, et al. Over expression of glutamate-eysteine ligase protects human COV434 granulosa tumour cells against oxidative and gammaradiation-induced cell death [J]. Mutagenesis, 2009, 24(3): 211-214.

[16] Faruk Abas, Tulin Alkan, Bulent Goren, et al. Neuroprotective effects of postconditioning on lipid pero- xidation and apoptosis after focal cerebral ischemia/reperfusion injury in rats[J]. Turk Neurosurg, 2010, 20(1): 1-8.

[17] Lin Jia-wei, Chen Juei-tai, Hong Chung-ye, et al. Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway[J]. Neuro Oncol, 2012, 14(3): 302-314.

[18] Vanessa Ginet, Julien Puyal, Peter G Clarke, et al. Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms[J]. Am J Pathol, 2009, 175(5): 1962-1974.

[19] Landa Zeenelabdin Ali Salim, Syam Mohan, Rozana Othman, et al. Thymoquinone induces mitochondria-mediated apop- tosis in acute lymphoblastic leukaemia in vitro[J]. Molecules, 2013, 18(9): 11219-11240.

大黄酚对小鼠脑缺血再灌注引起肝损伤的保护作用

Protective Effects of Chrysophanol on Liver Injury Induced by Cerebral Ischemia-Reperfusion in Mice

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