Rhynchophylline attenuates cerebral vasospasm after subarachnoid hemorrhage in rats

doi:10.3969/j.issn.0529-1356.2014.06.004

Abstract

Abstract:

Objective To investigate the effects of rhynchophylline (Rhy) on alleviating cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Methods SAH model was established in adult male SD rats by using endovascular perforation method. The Rhy was immediately applied by intraperitoneal injection after SAH. At 24hours after SAH, the diameter and vessel wall thickness of basilar artery (BA) were measured by magnetic resonance imaging (MRI) and/or HE staining. The levels of phosphorylated p38 mitogen-activated protein kinase（p-p38MAPK）, p-p53 and cleaved-Caspase-3 in BA were determined by Western blotting and immunofluorescence. Results After Rhy treatment, the diameter of BA was significantly increased and the thickness of vessel wall was markedly decreased （P<0.05）,Additionally, the levels of p-p38MAPK, p-p53 and cleaved-Caspase-3 in BA were significantly reduced by Rhy treatment after SAH（P<0.05）. Rhy can reduce the expression of BA p-p38 MAPK, p-p53, cleaved-Caspase-3 apoptosis protein in endothelial cell by immunofluorescence compared with SAH+NS group. Conclusion Rhy can attenuate CVS severty after SAH partly through eudothelial cell appotosis via p38MAPK-p53-Caspase-3 pathway.

Key words: Subarachnoid hemorrhage, Cerebral vasospasm, Basilar artery, Western blotting, Immunofluorescence, Rat

SUN Juan ZHANG Yan XU Ting YANG Lei ZHOU Chang-man LI Jian-hua* YAN Jun-hao*. Rhynchophylline attenuates cerebral vasospasm after subarachnoid hemorrhage in rats[J]. AAS, 2014, 45(6): 749-754.

References

［1］Biller J, Godersky JC, Adams HP. Management of aneurismal subarachnoid hemorrhage ［J］. Stroke,1988, 19(10): 1300-1305.
［2］Zhou C, Yamaguchi M, Colohan AR, et al. Role of p53 and apoptosis in cerebral vasospasm after experimental subarachnoid hemorrhage［J］. Cerebral Blood Flow Metab,2005,25(5):572-582.
［3］Iseda K, OnoS, Onoda K, et al. Antivasospastic and anti-inflammatory effects of caspase inhibitor in experimental subarachnoid hemorrhage［J］. Neurosurg,2007,107(1):128-135.
［4］Yan JH, Yang XM, Chen CH, et al. Pifithrin-alpha reduces cerebral vasospasm by attenuating apoptosis of endothelial cells in a subarachnoid haemorrhage model of rat［J］. Chin Med J (Engl), 2008,121(5):414-419.
［5］Liu J, Fu ZhJ. General sitution of the study on the Uncaria Rhynchophylla［J］. Strait Pharmaceutical Journal, 2006,8(5) B: 90-92.(in Chinese)
     刘佳,富志军.钩藤的研究概况［J］.海峡药学,2006,8(5)B:90-92.
［6］Shi JS, Yu JX, Chen XP, et al.Pharmacological actions of Uncaria alkaloids rhynchophyline and isorrhynchophyline ［J］.Acta Pharmacol Sin,2003, 24(2):97-101.
［7］Hu XY, Sun ASh, Yu LM, et al. Effects of Rhynchophylla total alkaloids on experimental cerebral ischemia ［J］. Chinese Pharmacological Bulletin,2004,20(11):1254-1256. (in Chinese)
     胡雪勇,孙安盛,余丽梅,等.钩藤总碱抗实验性脑缺血作用［J］.中国药理学通报,2004,20(11):1254-1256.
［8］Zhou J, Zhou S. Antihypertensive and neuroprotective activities of rhynchophyline in neurotransmission and ion channel activity ［J］. Ethnopharamacol, 2010,132(1):15-27.
［9］Wang M, Liu W. Research progress of total alkaloid extract of Uncaria Rhynchophylla ［J］. Practical Journal of Medicine & Pharmacy,2008,25(3)B :360-362. (in Chinese)
     王盟,刘卫.钩藤总生物碱的研究进展［J］.实用医药杂志,2008,25(3)B :360-362. 
［10］Yuan D, Ma B, Yang JY,et al. Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism ［J］. Int J Immunopharmacol,2009,9(13-14):1549-1554.
［11］Sasaki T, Kasuya H, Onda H, et al. Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage［J］.Stroke,2004, 35(6):1466-1470.
［12］Bederson JB, Germano IM, Guarino L. Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat［J］. Stroke,1995,26(6):1086-1091.
［13］Han H, Xia Z, Chen H, et al. Simple diffusion delivery via brain interstitial route for the treatment of cerebral ischemia［J］. Sci China Life Sci,2011, 54(3):235-239.
［14］Cahill J, Calvert JW, Solaroglu I, et al. Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage ［J］. Stroke,2006, 37(7):1868-1874.
［15］Gules I, Satoh M, Clower BR, et al. Comparison of three rat models of cerebral vasospasm ［J］. Am J Physiol Heart Circ Physiol,2002,283(6): H2551-H2559.
［16］Dietrich HH, Dacey RG Jr. Molecular keys to the problems of cerebral vasospasm ［J］. Neurosurgery,2000,46(3):517-530.
［17］Pyne-Geithman GJ, Morgan CJ, Wagner K, et al. Bilirub inproduction and oxidation in CSF of patients with cerebral vasospasm after subarachnoid hemorrhage［J］.Cereb Blood Flow Metab,2005,25(8):1070-1077.
［18］Faraci TM, Heistad DD. Regulation of the cerebral circulation: Role of endothelium and potassium channels ［J］. Physiol Rev,1998,78(1):53-97.
［19］Fassbender K, Hodapp B, Rossol S, et al. Inflammatory cytokines in subarachnoid hemorrhage: association with abnormal blood flow velocities in basal cerebral arteries ［J］.J Neurol Neurosurg Psychiatry, 2001, 70(4): 534-537.
［20］Wilkins RH. Cerebral vasospasm ［J］. Crit Rev Neurobiol,1990,6(1): 51-77.
［21］Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway ［J］. Cell Res,2005,15(1):11-18.
［22］Cory S, Adams JM. Killing cancer cells by flipping the Bcl-2/Bax switch ［ J］.Cancer Cell,2005,8(1):5-6.
［23］Wu EB, Hu XY, Sun ASh, et al. The antiapoptosis effects of rhynchophylla total alkaloids and coryadlis ambailis migo total alkaloids on cerebral ischemia/ reperfusion injury ［J］. Acta Academiae Medicinae Zunyi,2004,27(5):444-446. (in Chinese)
     吴二兵，胡雪勇，孙安盛，等. 夏天无、钩藤生物碱抗脑细胞凋亡作用及急性毒性［J］. 遵义医学院学报,2004,27(5):444-446.
［24］Heieh CL，Ho TY, Su SY, et al. Uncaria rhynchophylla and rhynchophylline inhibit c-Jun N- terminal kinase phosphorylation and nuclear factor-κB activity in kainic acid-treated rats［J］. Am J Chin Med,2009, 37(2):351-360.

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