Effects of hydroxysafflor yellow A on expression of MMP-9 and claudin-5 in cerebral ischemic/reperfusion rats

doi:10.3969/j.issn.1006-7795.2013.06.019

Abstract

Abstract:

Objective Hydroxysafflor yellow A(HSYA) is the water-extracted fraction from the flower of the safflower plant(C tinctorius), a traditional medicine, which has been used to treat ischemic diseases with a long history. Recent studies in rodents suggested that HSYA may reduce the blood brain barrier(BBB) permeability during acute cerebral ischemic/reperfusion. However, the mechanisms in BBB protection afforded by HSYA are still unclear. Methods In this study, we investigated the changes in protein level of matrix metalloproteinase-9(MMP-9) and tight junction protein claudin-5 in HSYA treatment on a 90 min-ischemia/72 h-reperfusion rat model, which mimics the possible clinical application for acute ischemic stroke patients. Results Western blotting indicated that HSYA reduced the MMP-9 level but increased the level of claudin-5 in penumbral tissue. However, there is no significant change in MMP-9 and claudin-5 level in ischemic core. Conclusion The reduction of MMP-9 and elevation of claudin-5 in penumbral might be involved in HSYA afforded BBB protection on ischemic/reperfusion model of rats.

Key words: cerebral ischemia, hydroxysafflor yellow A, metalloproteinase-9, claudin-5, blood brain barrier

CLC Number:

R743.31

QI Zhifeng, SHI Wenjuan, YAN Feng, LUO Yumin, LIU Kejian. Effects of hydroxysafflor yellow A on expression of MMP-9 and claudin-5 in cerebral ischemic/reperfusion rats[J]. Journal of Capital Medical University, 2013, 34(6): 879-884.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2013.06.019

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2013/V34/I6/879

References

[1] Nie P H, Zhang L, Zhang W H, et al. The effects of hydroxysafflor yellow A on blood pressure and cardiac function[J]. J.Ethnopharmacol, 2012, 139(3):746-750.
[2] Sun L, Yang L, Xu Y W, et al. Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia: inhibition of protein oxidation/nitration, 12/15-lipoxygenase and blood-brain barrier disruption[J]. Brain Res, 2012, 1473:227-235.
[3] Zhu H B, Wang Z H, Tian J W, et al. Protective effect of hydroxysafflor yellow A on experimental cerebral ischemia in rats[J]. YaoXueXueBao, 2005, 40(12):1144-1146.
[4] Zang B X, Jin M, Si N, et al. Antagonistic effect of hydroxysafflor yellow A on the platelet activating factor receptor[J]. YaoXueXueBao, 2002, 37(9):696-699.
[5] Liu Y N, Zhou Z M, Chen P. Evidence that hydroxysafflor yellow A protects the heart against ischaemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening[J]. Clin Exp Pharmacol Physiol, 2008, 35(2):211-216.
[6] He H, Yang X, Shi M, et al. Protective effects of hydroxysafflor yellow A on acute and chronic congestive cardiac failure mediated by reducing ET-1, NOS and oxidative stress in rats[J]. J Pharm Pharmacol, 2008, 60(1):115-123.
[7] Liu K J, Rosenberg G A. Matrix metalloproteinases and free radicals in cerebral ischemia[J]. Free Radic Biol Med, 2005, 39(1):71-80.
[8] Qi Z F, Luo Y M, Liu X R, et al. AKT/GSK3beta-dependent autophagy contributes to the neuroprotection of limb remote ischemic postconditioning in the transient cerebral Ischemic rat model[J]. CNS Neurosci Ther, 2012, 28:965-973.
[9] Fisher M, Bastan B. Identifying and utilizing the ischemic penumbra[J]. Neurology, 2012, 79(13 suppl):S79-S85.
[10] Liu S, Shi H, Liu W, et al. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats[J]. J Cereb Blood Flow Metab, 2004, 24(3):343-349.
[11] Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury[J]. Stroke, 2011, 42(6):1781-1786.
[12] Eltzschig H K, Eckle T. Ischemia and reperfusion-from mechanism to translation[J]. Nat Med, 2011, 17(11):1391-1401.
[13] Shah K, Abbruscato T. The Role of Blood-brain barrier transporters in pathophysiology and pharmacotherapy of stroke[J]. Curr Pharm Des, 2013, Jun 19..
[14] Hawkins B T, Davis T P. The blood-brain barrier/neurovascular unit in health and disease[J]. Pharmacol Rev, 2005, 57(2):173-185.
[15] Yang Y, Rosenberg G A. MMP-mediated disruption of claudin-5 in the blood-brain barrier of rat brain after cerebral ischemia[J]. Methods Mol Biol, 2011, 762:333-345.
[16] Hernandez-Guillamon M, Martinez-Saez E, Delgado P, et al. MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke[J]. Brain Pathol, 2011, 22(2):133-141.
[17] Ramos-Fernandez M, Bellolio M F, Stead L G. Matrix metalloproteinase-9 as a marker for acute ischemic stroke: a systematic review[J]. J Stroke Cerebrovasc Dis, 2011, 20(1):47-54.
[18] Tian J, Li G, Liu Z, et al. Hydroxysafflor yellow A inhibits rat brain mitochondrial permeability transition pores by a free radical scavenging action[J]. Pharmacology, 2008, 82(2):121-126.
[19] Rosenberg G A, Estrada E Y, Dencoff J E. Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain[J]. Stroke, 1998, 29(10):2189-2195.
[20] Lakhan S E, Kirchgessner A, Tepper D, et al. Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke[J]. Front Neurol, 2013, 4:32.
[21] Asahi M, Wang X, Mori T, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia[J]. J Neurosci, 2001, 21(19):7724-7732.
[22] Svedin P, Hagberg H, Savman K, et al. Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia[J]. J Neurosci, 2007, 27(7):1511-1518.