Effects of Paeoniflorin on ATPase and EAA in Gerbils with Cerebral Ischemia/Reperfusion Injury

Abstract

Abstract: ObjectiveTo investigate the effects of paeoniflorin (PAE) on gerbils with cerebral ischemia/reperfusion (CI/R) injury and the mechanisms involved. MethodsGerbil model of CI/R was prepared by bilateral common carotid occlusion for 10 min followed by 6-hour reperfusion. Then gerbils were divided into 5 groups at random (n=10), namely sham, model, PAE high, medium and low dose groups (20, 10 and 5 mg·kg-1, respectively). PAE was injected intraperitoneally(i.p.) for 3 days before the carotid occlusion. Stroke index was calculated during the reperfusion. The ATPase activities in brain tissue homogenate were examined by a phosphate assay and glutamate (Glu) and aspirate (Asp) contents were determined by HPLC. ResultsThe results showed that PAE significantly improved stroke index, compared to the model group (P <0.05 or P <0.01). PAE evidently elevated Ca2+-ATPase activities in brain tissue of CI/R gerbils (P <0.05). The Na+-K+-ATPase activities in PAE high and medium dose groups were significantly higher than the model group (P <0.05 or P <0.01). PAE markedly inhibited the Glu contents in brain tissue of CI/R gerbils (P <0.05 or P <0.01). However, PAE showed no influence on Mg2+-ATPase activities or Asp contents in brain tissue. ConclusionThe effectiveness of PAE pretreatment in CI/R injury appears to be associated with the enhancement of ATPase activities and inhibition of excitatory amino acid (EAA) toxicity in brain tissue.

Key words: paeoniflorin, cerebral ischemia/reperfusion injury, ATPase, excitatory amino acid(EAA)

CLC Number:

R965

LI Dong-mei, CHE Wei, LI Xia, CAO Jun-ping. Effects of Paeoniflorin on ATPase and EAA in Gerbils with Cerebral Ischemia/Reperfusion Injury[J]. Chinese Journal of Pharmacovigilance, 2014, 11(12): 717-720.

References

[1] Lu C, Hua F, Liu L, et al. Scavenger receptor class-A has a central role in cerebral ischemia-reperfusion injury[J]. J Cereb Blood Flow Metab, 2010, 30(12): 1972-1981.
[2] Siesj B K, Zhao Q, Pahlmark K, et al. Glutamate, calcium, and free radicals as mediators of ischemic brain damage[J]. Ann Thorac Surg, 1995, 59(5): 1316-1320.
[3] Chi OZ, Hunter C, Liu X, et al. Effects of exogenous excitatory amino acid neurotransmitters on blood-brain barrier disruption in focal cerebral ischemia[J].Neurochem Res, 2009, 34(7): 1249-1254.
[4] 李茜,陈兴东,段满林.急性脑缺血对机体免疫系统的影响[J].医学研究生学报,2013,26(6)：654-657．
[5] 孙丽荣,曹雄,侯凤青,等.芍药苷研究进展[J].中国中药杂志,2008,33(18)：2028-2032．
[6] Zhang M H, Feng L, Zhu M M, et al. Antioxidative and anti-inflammatory activities of paeoniflorin and oxypaeoniflora on AGEs-induced mesangial cell damage[J]. Planta Med, 2013, 79(14): 1319-1323.
[7] 胡增峣 ,徐岚,闫蓉,等.芍药苷作用于神经系统的研究进展[J].中国中药杂志,2013,38(3)：297-301．
[8] Kapoor S. Neuroprotective effects of paeoniflorin: an emerging concept in neurology[J]. Folia Neuropathol, 2013, 51(1): 92.
[9] Xiao L, Wang Y Z, Liu J, et al. Effects of paeoniflorin on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of transient middle cerebral artery occlusion in rats[J]. Life Sci, 2005, 78(4): 413-420.
[10] Liu D Z, Xie K Q, Ji X Q, et al. Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists[J]. Br J Pharmacol, 2005, 146(4): 604-611.
[11] Guo R B, Wang G F, Zhao A P, et al. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses[J]. PLoS One, 2012, 7(11): e49701.
[12] 刘静.芍药甙对动物全脑缺血的保护作用及其机制研究[D].上海：中国科学院上海药物研究所博士学位论文,2006：24.
[13] Chen Q, Zeng Y M, Xu P C, et al. Influence of batroxobin on cerebral ischemia-reperfusion injury in gerbils[J]. Acta Pharmacol Sin, 2000, 21(2): 161-164.
[14] Ito U, Hakamata Y, Yamaguchi T, et al. Cerebral ischemia model using mongolian gerbils-comparison between unilateral and bilateral carotid occlusion models[J]. Acta Neurochir Suppl, 2013, 118(1): 17-21.
[15] Chen B M, Xia L M, Zhao R Q. Determination of NG, NG-dime-thylarginine in human plasma by high-performance liquid chromatography[J]. Journal of Chromatography B, 1997, 692(2): 467-471.
[16] 夏强,钱令波.心脑缺血再灌注损伤的机制及防治策略研究进展[J].浙江大学学报：医学版,2010,39(6)：551-558．
[17] Jorgensen P L, Pedersen P A. Structure-function relationships of Na+, K+, ATP, or Mg2+ binding and energy transduction in Na, K-ATPase[J]. Biochim Biophys Acta, 2001, 1505(1): 57-74.
[18] Jung Y W, Choi I J, Kwon T H. Altered expression of sodium transporters in ischemic penumbra after focal cerebral ischemia in rats[J]. Neurosci Res, 2007, 59(2): 152-159.
[19] 冯国清,吴红霞,王振基,等.前列腺素E1对脑缺血再灌注损伤的保护作用[J].中国药理学通报,2003,19(4)：427-431．
[20] Koizumi H, Fujisawa H, Suehiro E, et al. Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide[J]. Neurol Med Chir, 2011, 51(5): 337-343.
[21] Bie X, Chen Y, Han J, et al. Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum[J]. Asia Pac J Clin Nutr, 2007, 16（1）: 305-308.
[22] Chao X D, Fei F, Fei Z. The role of excitatory amino acid transporters in cerebral ischemia [J]. Neurochem Res, 2010, 35(8): 1224-1230.
[23] 张焰,陈群,顾卫东,等.灯盏花素对缺血再灌注沙土鼠海马ATP含量变化和兴奋性氨基酸释放的影响[J].江苏医药,2005,31(11)：843-845．
[24] Kuang P, Xiang J. Effect of radix salviae miltiorrhizae on EAA and IAA during cerebral ischemia in gerbils: a microdialysis study [J]. J Tradit Chin Med, 1994, 14(1): 45-50.
[25] Saleem S, Ahmad M, Ahmad A S, et al. Effect of Saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats[J]. J Med Food, 2006, 9(2): 246-253.