题名

Effects of Baicalin on Protease-Activated Receptor-1 Expression and Brain Injury in a Rat Model of Intracerebral Hemorrhage

DOI

10.4077/CJP.2012.BAA050

作者

Qing-Bo Zhou;Qing Jia;Yuan Zhang;Lu-Yang Li;Zhao-Fu Chi;Ping Liu

关键词

baicalin ; intracerebral hemorrhage ; protease-activated receptor ; neuroprotection

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

55卷3期(2012 / 06 / 01)

页次

219 - 226

内容语文

英文

英文摘要

Baicalin, a major flavonoid compound isolated from the dry roots of Scutellaria baicalensis Georgi, has been shown to be neuroprotective after ischemic brain injury. However, little is known about its effects on brain injury following intracerebral hemorrhage (ICH). In this study, we evaluated the effects of baicalin on ICH-induced brain injury in an ICH rat model. Male Wistar rats were injected intracerebrally with 0.5 U collagenaseVII to induce ICH, while control rats were injected with an equal volume of saline. After ICH induction, the rats were randomly divided into four groups and treated with baicalin at different doses (0, 25, 50 or 100 mg/kg) through peritoneal injection. The control rats were injected with an equal volume of vehicle. Brain tissues around the hemorrhage areas were collected on day 1, 3, 5 and 10 after treatment. Brain water content was analyzed by desiccation method; mRNA and protein levels of brain protease-activated receptor-1 (PAR-1) were determined by RT-PCR and Western blot, respectively; cell apoptosis was evaluated by terminal transferase dUTP nick end labeling staining. The results showed that baicalin effectively attenuated brain edema and inhibited cell apoptosis following ICH in a dose- and time-dependent manner, with concomitant suppression of PAR-1 expression at both the mRNA and protein levels. These findings indicate that baicalin has protective effects on ICH-induced brain injury. The effects of baicalin may involve a mechanism of inhibition of PAR-1 expression.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Bartha, K.,Domotor, E.,Lanza, F.,Adam-vizi, V.,Machovich, R.(2000).Identification of thrombin receptors in rat brain capillary endothelial cells.J. Cereb. Blood Flow Metab.,20,175-182.
  2. Cao, Y. G.,Mao, X. Y.,Sun, C. Y.,Zheng, P.,Gao, J. Q.,Wang, X. R.,Min, D. Y.,Sun, H. L.,Xie, N.,Cai, J. Q.(2011).Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways.Brain Res. Bull.,85(6),396-402.
  3. Chomczynski, P.,Sacchi, N.(1987).Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem.,162,156-159.
  4. Gao, Z.,Huang, K.,Xu, H.(2001).Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells.Pharmacol. Res.,43,173-178.
  5. Ge, Q. F.,Hu, X.,Ma, Z. Q.,Liu, J. R.,Zhang, W. P.,Chen, Z.,Wei, E. Q.(2007).Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA receptor-mediated 5-lipoxygenase activation in rat cortical neurons.Pharmacol. Res.,2,148-157.
  6. Gong, C.,Boulis, N.,Qian, J.,Turner, D. E.,Hoff, J. T.,Keep, R. F.(2001).Intracerebral hemorrhage-induced neuronal death.Neurosurgery,48,875-882.
  7. Hua, Y.,Keep, R. F.,Hoff, J. T.,Xi, G.(2007).Brain injury after intracerebral hemorrhage: the role of thrombin and iron.Stroke,38,759-762.
  8. Ikezoe, T.,Chen, S. S.,Heber, D.,Taguchi, H.,Koeffler, H. P.(2001).Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest.Prostate,49,285-292.
  9. Kitaoka, T.,Hua, Y.,Xi, G.,Hoff, J. T.,Keep, R. F.(2002).Delayed argatroban treatment reduces edema in a rat model of intracerebral hemorrhage.Stroke,33,3012-3018.
  10. Lee, K. R.,Colon, G. P.,Betz, A. L.,Keep, R. F.,Kim, S.,Hoff, J. T.(1996).Edema from intracerebral hemorrhage: the role of thrombin.J. Neurosurg.,84,91-96.
  11. Lee, K. R.,Kawai, N.,Kim, S.,Sagher, O.,Hoff, J. T.(1997).Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model.J. Neurosurg.,86,272-278.
  12. Liu, L. Y.,Wei, E. Q.,Zhao, Y. M.,Chen, F. X.,Wang, M. L.,Zhang, W. P.,Chen, Z.(2005).Protective effects of baicalin on oxygen/glucose deprivation- and NMDA-induced injuries in rat hippocampal slices.J. Pharm. Pharmacol.,8,1019-1026.
  13. Liu, P.,Wang, J. Y.,Wang, Z. Y.,Xu, F. Y.,Liu, Z. P.,Zhang, X. M.(2005).Effects of baicalin on hippocampus neuronal apoptosis in focal cerebral ischemia-reperfusion injury rats.Chinese J. Pharmacol. Toxicol.,19,412-418.
  14. Liu, P.,Zhang, X. M.,Wang, J. Y.,Li, Q.,Wang, Z. Y.,Xu, F. Y.,Ma, J. F.,Liu, Z. P.(2007).Protective effect of baicalin on focal cerebral ischemia-reperfusion injury in rats.J. Chin. Pharm.,10,743-748.
  15. Mayne, M.,Ni, W.,Yan, H. J.,Xue, M.,Johnston, J. B.,Del Bigio, M. R.,Peeling, J.,Power, C.(2001).Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-α expression is neuroprotective after intracerebral hemorrhage.Stroke,32,240-248.
  16. Naldini, A.,Pucci, A.,Carney, D. H.,Fanetti, G.,Carraro, F.(2002).Thrombin enhancement of interleukin-1 expression in mononuclear cells: involvement of proteinase-activated receptor-1.Cytokine,20,191-199.
  17. Naval, N. S.,Nyquist, P. A.,Carhuapoma, J. R.(2008).Management of spontaneous intracerebral hemorrhage.Neurol. Clin.,26,373-384.
  18. Ouyang, C. H.,Wu, J. L.(2006).Protective effect of baicalin on inflammatory injury following transient focal cerebral ischemiareperfusion in rats.Chinese J. Pharmacol. Toxicol.,20,288-294.
  19. Rodrigues, C. M.,Sola, S.,Nan, Z.,Castro, R. E.,Ribeiro, P. S.,Low, W. C.,Steer, C. J.(2003).Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats.Proc. Natl. Acad. Sci.,10,6087-6092.
  20. Rosenberg, G. A.,Mun-Bryce, S.,Wesley, M.,Kornfeld, M.(1990).Collagenase-induced intracerebral hemorrhage in rats.Stroke,21,801-807.
  21. Shen, Y. C.,Chiou, W. F.,Chou, Y. C.,Chen, C. F.(2003).Mechanisms in mediating the antiinflammatory effects of baicalin and baicalein in human leukocytes.Eur. J. Pharmacol.,465,171-181.
  22. Strande, J. L.,Phillips, S. A.(2009).Thrombin increases inflammatory cytokine and angiogenic growth factor secretion in human adipose cells in vitro.J. Inflamm. (Lond).,6,4.
  23. Terai, K.,Suzuki, M.,Sasamata, M.,Miyata, K.(2003).Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.Neurochem. Res.,28,779-785.
  24. Tian, H.,Zhang, X.,Wu, C.,Chen, L.,Ying, R. C.,Ye, J.,Yu, B. Y.,Ye, Q.,Pan, Y.,Ma, M. L.(2009).Effects of baicalin and octreotide on the serum TNF-α level and apoptosis in multiple organs of rats with severe acute pancreatitis.Inflammation,32,191-201.
  25. Xi, G.,Keep, R. F.,Hoff, J. T.(2006).Mechanisms of brain injury after intracerebral hemorrhage.Lancet Neurol.,5,53-63.
  26. Xi, G.,Keep, R. F.,Hua, Y.,Hoff, J. T.(1999).Attenuation of thrombininduced brain edema by cerebral thrombin preconditioning.Stroke,30,1247-1255.
  27. Xi, G.,Reiser, G.,Keep, R. F.(2003).The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective.J. Neurochem.,84,3-9.
  28. Xu, G.,Dou, J.,Zhang, L.,Guo, Q.,Zhou, C.(2010).Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the Serum.Biol. Pharm. Bull.,33,238-243.
  29. Xue, M.,Del Bigio, M. R.(2001).Acute tissue damage after injections of thrombin and plasmin into rat striatum.Stroke,32,2164-2169.
  30. Xue, M.,Hollenberg, M. D.,Chapman, K.,Demchuk, A.,Yong, V. W.(2009).Relative importance of proteinase-activated receptor-1 versus matrix metalloproteinases in intracerebral hemorrhagemediated neurotoxicity in mice.Stroke,40,2199-2204.
  31. Xue, M.,Hollenberg, M. D.,Yong, V. W.(2006).Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity in cell culture and intracerebral hemorrhage in mice.J. Neurosci.,26,10281-10291.
  32. Xue, X.,Qua, X. J.,Yang, Y.,Sheng, X. H.,Cheng, F.,Jiang, E. N.,Wang, J. H.,Bu, W.,Liu, Z. P.(2010).Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor κB p65 activation.Biochem. Bioph. Res. Comm.,403,398-404.
  33. Yang, S.,Song, S.,Hua, Y.,Nakamura, T.,Keep, R. F.,Xi, G.(2008).Effects of thrombin on neurogenesis after intracerebral hemorrhage.Stroke,39,2079-2084.
  34. Zheng, G. Q.,Wang, X. T.,Wang, X. M.,Guo, R. R.,Zeng, X. L.,Fu, X. L.,Wang, Y.(2009).Long-time course of protease-activated receptor-1 expression after intracerebral hemorrhage in rats.Neurosci. Lett.,459,62-65.
  35. Zhong, C.,Hayzer, D. J.,Corson, M. A.,Runge, M. S.(1992).Molecular cloning of the rat vascular smooth muscle thrombin receptor. Evidence for in vitro regulation by basic fibroblast growth factor.J. Biol. Chem.,267,16975-16979.
  36. Zhou, Q. B.,Li, L. Y.,Jia, Q.,Zheng, G. J.,Bi, J. Z.,Shao, N. F.(2007).Protective effect of Naoningkang granula on intracerebral hemorrhage rats.Chinese J. Integr. Trad. West. Med.,27,814-818.