Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury<sup>△</sup>

Kong Xiangyi; Guan Jian; Gong Shun; Wang Renzhi

doi:10.24920/J1001-9294.2017.020

Your Location：

Home >

Browse articles >

Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury^△

Chinese Medical Sciences Journal Vol. 32, Issue 2, Pages: 92-99(2017)

Orginal Article | Updated：2024-04-10

- Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury^△
- Affiliations：
  
  1. 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
  2. 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Massachusetts 02114, USA
  3. 3Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  4. 4Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Massachusetts 02215, USA
- Author bio：
  
  *Corresponding author Tel: 86-10-69152530, Fax: 86-10-69152530, E-mail: wrzpumch@163.com
- Funds：
- DOI：10.24920/J1001-9294.2017.020
  CLC：
- Received：17 February 2017，
  
  Published Online：20 June 2017，
  
  Published：2017-06
- Accepted：
Scan QR Code
Kong Xiangyi, Guan Jian, Gong Shun, et al. Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury^△[J]. Chinese medical sciences journal, 2017, 32(2): 92-99.
DOI：

Kong Xiangyi, Guan Jian, Gong Shun, et al. Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury^△[J]. Chinese medical sciences journal, 2017, 32(2): 92-99. DOI： 10.24920/J1001-9294.2017.020.

摘要

目的

氧化应激（oxidative stress

OS）在缺血性脑卒中病程中起到关键作用。葡萄籽原花青素提取物（grape seed procyanidin extract

GSPE）是OS的重要调节剂。我们猜想GSPE可以保护缺血缺氧性脑损伤。本研究旨在探索GSPE能否在小鼠的缺血再灌注脑损伤起保护作用。

方法

对于接受GSPE注射（MCAOG

n=60）和生理盐水注射（MCAONS

n=60）的小鼠

制作短暂性大脑中动脉栓塞（transient middle cerebral artery occlusion

MCAO）模型。设置假手术组小鼠（GSPE组和生理盐水组）作为对照。采用改良的神经损害评分（mNSS）评估并比较MCAO造模后1小时、24小时、3天、7天的神经功能损害情况。在MCAO造模24小时后行3T动物颅脑核磁共振（T2WI）扫描

评估并比较梗死灶体积差异。在MCAO造模24小时后

对脑组织行神经元细胞核抗体（NeuN）、CD34、Bcl-2和Bax

以及脑组织中谷胱甘肽过氧化物酶（glutathione peroxidation

GSH-Px)）和丙二醛（MDA）进行免疫组化分析。对以上指标都在各组之间的差异进行统计学分析。

结果

在MCAO造模24小时及之后

MCAOG组小鼠神经功能恢复好于MCAONS组小鼠（p

0.05）在MCAO造模24小时

MCAOG组小鼠脑梗塞灶体积明显小于MCAONS组小鼠（22.46 ± 11.45 mm

vs.

47.84 ± 9.06 mm

0.05）;MCAOG小鼠梗塞灶周边区域NeuN和CD34阳性染色细胞数目明显多于MCAONS小鼠（p

0.05）。MCAONS组小鼠Bax阳性染色细胞数目明显多于MCAOG组（p

0.05）。MCAOG组小鼠脑组织中平均MDA水平明显低于MCAONS组（

0.05）

GSH-Px活力明显高于MCAONS组（p

0.05）。

结论

GSPE可抑制小鼠缺血再灌注脑损伤的病程。其机制可能与GSPE抑制了病程中氧化应激和凋亡反应

促进了微血管生成

以及激活抗氧化酶（GSH-Px）有关。GSPE可能代表了一种治疗缺血再灌注脑损伤的新方向。

Abstract

Objective

Oxidative stress (OS) plays a crucial role in ischemic stroke. Grape seed procyanidin extract (GSPE) was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury.

Methods

Transient middle cerebral artery occlusion (MCAO) was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE (MCAOG

n=60) or normal saline (MCAONS

n=60). Sham-operated mice (GSPE group and normal saline group) were set as controls. The neurological severity score (NSS) was used to evaluate neural function impairment 1 hour

24 hour

3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion

and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen (NeuN)

CD34

Bcl-2

and Bax. Glutathione peroxidation (GSH-Px) activity and the level of malonaldehyde (MDA) of brain tissue were also examined. The above indexes were compared among the groups statistically.

Results

Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group (

0.05). MCAOG group had smaller cerebral stroke volume (22.46 ± 11.45 mm

vs.

47.84±9.06 mm

0.05) than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice (both

0.05). MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG (

0.05). The mean MDA level was significantly lower (

0.05) and the GSH-Px activity was significantly higher (

0.05) in brains of MCAOG mice compared to those of MCAONS mice.

Conclusion

GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis

promoting angiogenesis

and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.

关键词

Keywords

references

Feigin VL. Stroke epidemiology in the developing world. Lancet 2005 ; 365 : 2160 - 1 . doi: 10.1016/S0140-6736 (05)66755-4 10.1016/S0140-6736 (05)66755-4 .

Allen CL , Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke 2009 ; 4 : 461 - 70 . doi: 10.1111/j.1747-4949.2009.00387.x 10.1111/j.1747-4949.2009.00387.x .

Moskowitz MA , Lo EH , Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron 2010 ; 67 : 181 - 98 . doi: 10.1016/j.neuron.2010.07.002 10.1016/j.neuron.2010.07.002 .

Chen T , Liu W , Chao X , et al. Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: involvement of mitogen-activated protein kinase pathway. Neuroscience 2011 ; 183 : 203 - 11 . doi: 10.1016/j.neuroscience.2011.03.038 10.1016/j.neuroscience.2011.03.038 .

Mehlomakulu NN , Prior KJ , Setati ME , et al. Candida pyralidae killer toxin disrupts the cell wall of Brettanomyces bruxellensis in red grape juice. J Appl Microbiol 2017 ; 122 : 747 - 58 . doi: 10.1111/jam.13383 10.1111/jam.13383 .

Chen Q , Zhang R , Li WM , et al. The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice. Environ Toxicol Pharmacol 2013 ; 36 : 759 - 68 . doi: 10.1016/j.etap.2013.07. 006 10.1016/j.etap.2013.07. 006 .

Chen J , Li Y , Wang L , et al. Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats. Stroke 2001 ; 32 : 1005 - 11 . doi: 10.1161/01.STR.32.4.1005 10.1161/01.STR.32.4.1005 .

Gauvrit JY , Leclerc X , Pernodet M , et al. Value of MRI in the etiologic diagnosis of cerebral infarction. J Radiol 2005 ; 86 : 1080 - 9 .

Pillai DR , Dittmar MS , Baldaranov D , et al. Cerebral ischemia-reperfusion injury in rats-a 3 T MRI study on biphasic blood-brain barrier opening and the dynamics of edema formation. J Cereb Blood Flow Metab 2009 ; 29 : 1846 - 55 . doi: 10.1038/jcbfm.2009.106 10.1038/jcbfm.2009.106 .

Liu F , Schafer DP , Mccullough LD. TTC, fluoro-Jade B and NeuN staining confirm evolving phases of infarction induced by middle cerebral artery occlusion. J Neurosci Methods 2009 ; 179 : 1 - 8 . doi: 10.1016/j.jneumeth.2008. 12.028 10.1016/j.jneumeth.2008. 12.028 .

Kong X , Guan J , Ma W , et al. CD34 Over-expression is associated with Gliomas' higher WHO grade. Medicine (Baltimore) 2016 ; 95 : e2830 . doi: 10.1097/MD.0000000 000002830 10.1097/MD.0000000 000002830 .

Bizzi I , Ghezzi P , Paudyal P. Health information quality of websites on periodontology. J Clin Periodontol 2017 ; 44 : 308 - 14 . doi: 10.1111/jcpe.12668 10.1111/jcpe.12668 .

Hattori K , Lee H , Hurn PD , et al. Cognitive deficits after focal cerebral ischemia in mice. Stroke 2000 ; 31 : 1939 - 44 .

Zanolin ME , Girardi P , Degan P , et al. Measurement of a urinary marker (8-hydroxydeoxy-guanosine, 8-OHdG) of DNA oxidative stress in epidemiological surveys: a pilot study. Int J Biol Markers 2015 ; 30 : e341 - 5 . doi: 10.5301/ jbm.5000129 10.5301/ jbm.5000129 .

Liu G , Wang T , Wang T , et al. Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats. Biomed Rep 2013 ; 1 : 861 - 7 . doi: 10.3892/br.2013. 153 10.3892/br.2013. 153 .

Zhang JQ , Gao BW , Wang J , et al. Critical role of FoxO1 in granulosa cell apoptosis caused by oxidative stress and protective effects of grape seed procyanidin B2. Oxid Med Cell Longev 2016 ; 2016 : 6147345 . doi: 10.1155/2016/ 6147345 10.1155/2016/ 6147345 .

Terra X , Montagut G , Bustos M , et al. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 2009 ; 20 : 210 - 8 . doi: 10.1016/j.jnutbio.2008.02. 005 10.1016/j.jnutbio.2008.02. 005 .

Jin H , Liu M , Zhang X , et al. Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation. J Nutr Biochem 2016 ; 36 : 81 - 8 . doi: 10.1016/j.jnutbio.2016.07.006 10.1016/j.jnutbio.2016.07.006 .

Yamakoshi J , Saito M , Kataoka S , et al. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol 2002 ; 40 : 599 - 607 .

Shahjouei S , Cai PY , Ansari S , et al. Middle cerebral artery occlusion model of stroke in rodents: A step-by-step approach. J Vasc Interv Neurol 2016 ; 8 : 1 - 8 .

Aleu A , Mellado P , Lichy C , et al. Hemorrhagic complications after off-label thrombolysis for ischemic stroke. Stroke 2007 ; 38 : 417 - 22 . doi: 10.1161/01.STR.0000254 504.71955.05 10.1161/01.STR.0000254 504.71955.05 .

Kowalczuk K , Stryjecka-Zimmer M. The influence of oxidative stress on the level of malondialdehyde (MDA) in different areas of the rabbit brain. Ann Univ Mariae Curie Sklodowska Med 2002 ; 57 : 160 - 4 .

Olsvik PA , Kristensen T , Waagbo R , et al. mRNA expression of antioxidant enzymes (SOD, CAT and GSH-Px) and lipid peroxidative stress in liver of Atlantic salmon (Salmo salar) exposed to hyperoxic water during smoltification. Comp Biochem Physiol C Toxicol Pharmacol 2005 ; 141 : 314 - 23 . doi: 10.1016/j.cbpc.2005.07.009 10.1016/j.cbpc.2005.07.009 .

Pallares V , Fernandez-Iglesias A , Cedo L , et al. Grape seed procyanidin extract reduces the endotoxic effects induced by lipopolysaccharide in rats. Free Radic Biol Med 2013 ; 60 : 107 - 14 . doi: 10.1016/j.freeradbiomed.2013.02.007 10.1016/j.freeradbiomed.2013.02.007 .

Views

1598

Downloads

CSCD

Alert me when the article has been cited

Submit

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰