Ratlarda Deneysel Subaraknoidal Kanama Sonrası Gelişen Serebral Vazospazmın, Seleritrin Kullanılarak Engellenmesi

Yıl 2017, Cilt: 6 Sayı: 1, 18 - 22, 01.04.2017

M Arif Aladag Azibe Yıldız Yusuf Turkoz Hakan Parlakpınar

Öz

Amaç: Önlenmesi için büyük çapta deneysel ve klinik araştırmalar yapılmış olmasına rağmen, anevrizmal subaraknoidal kanamanın SAK yıkıcı bir tıbbi komplikasyonu olan serebral vazospazm, yüksek oranda morbidite ve mortalite ile birliktedir. Deneysel sonuçların çoğu güçlü vazokonstrüktör protein kinaz C’nin PKC serebral vazospazmda anahtar bir rol oynadığı görüşünü desteklemektedir. Biz vazospazmı önlemek için, deneysel subaraknoidal kanama modelinde güçlü, selektif ve hücre içine geçebilen protein kinaz C PKC inhibitörünü seleritrin klorid sistemik olarak kullandık. Materyal ve Yöntem: Yirmi sekiz sıçan dört gruba ayrıldı: grup 1 kontrol grubu; grup 2, SAK grubu, grup 3, SAK artı plasebo grubu; ve grup 4, SAK artı chelerythrine chloride 5 µmol /kg/gün grubu ayrıldı. 3. ve 4. gruplara Seleritrin klorid veya eşit hacimde % 0.9 salin sırasıyla, intraperitoneal olarak 5 gün süreyle verildi. Sıçanlar beşinci günde sakrifiye edildi. Kesitler ışık mikroskobu ile incelendi. Pons seviyesinde yapılan kesitlerde, baziler arterin lümen alanı ve duvar kalınlığı ölçümleri mikrometre ile alındı. Bulgular: 4. gruptaki baziler arter daralması 2 ve 3 gruplarla karşılaştırıldığında, önemli ölçüde p

Anahtar Kelimeler

Sıçan, Subaraknoidal Kanama, Vazospazm, PKC İnhibitörü

The Inhibition of Cerebral Vasospasm by Using Chelerythrine After Experimental Subarachnoidal Haemorrhage in Rats

Öz

Background: Cerebral vasospasm, a devastating medical complication of aneurysmal subarachnoid hemorrhage SAH , is associated with high morbidity and mortality although a great deal of experimental and clinical research conducted to prevent this complication. The most of the experimental results support the view that potent vasoconstrictor proteine kinase C PKC , plays a key factor in cerebral vasospasm. To inhibit vasospasm, we used a potent, selective, and cell-permeable protein kinase C PKC inhibitor chelerythrine chloride systemically in an experimental subarachnoidal hemorrhage SAH model. Methods: Twenty eight rats were divided into four groups: group 1; control, group 2; SAH, group 3; SAH plus placebo, and group 4; SAH plus chelerythrine chloride 5 µmol/kg/day . Chelerythrine chloride or an equal volume of 0.9 % saline was intraperitoneally administered for 5 days to groups 3 and 4, respectively. The rats were sacrificed on the fifth day. Sectioned slices were examined by light microscopy. Measurements were made for the cross-sectional areas of the lumen and the vessel wall of basilar artery in the sections of pons by a micrometer. Findings: The vasoconstriction of the basilar artery significantly attenuated in group 4 compared with the groups 2 and 3 p

Anahtar Kelimeler

Rat, Subarachnoid Haemorrhage, Vasospasm, PKC Inhibitor

Kaynakça

• Nishizawa S, Chen D, Yokoyama T. et al. Endothelin-1 initiates the development of vasospasm after subarachnoid haemorrhage through protein kinase c activation, but does not contribute to prolonged vasospasm. Acta Neurochir (Wien) 2000; 142: 1409- 15.
• Laher I, Zhang JH. Protein Kinase C and Cerebral Vasospasm J Cereb Blood Flow Metab 2001; 21(8):887-906.
• Nishizawa S, Obara K, Nakayama K. et al. Protein kinase c delta and alpha are involved in the development of vasospasm after subarachnoid hemorrhage. Eur J Pharmacol 2000; 398:113–9.
• Hu N, Wu Y, Chen BZ. et al. Protective effect of stellate ganglion block on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. Brain Res 2014; 1585: 63-71.
• Siuta M, Zuckerman SL, Mocco J. Nitric oxide in cerebral vasospasm: theories, measurement, and treatment. Neurol Res Int 2013;2013:972417.
• Miller BA, Turan N, Chau M. et al. Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage. Biomed Res Int 2014; 2014:384342.
• Huang CY, Wang LC, Shan YS. et al. Memantine attenuates delayed vasospasm after experimental subarachnoid hemorrhage via modulating endothelial nitric oxide synthase. Int J Mol Sci 2015; 16:14171-80.
• Laban KG, Vergouwen MD, Dijkhuizen RM. et al. Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab 2015; 35: 1085-9.
• Chang CZ, Wu SC, Kwan AL. Glycyrrhizin attenuates Toll like receptor-2, −4 and experimental vasospasm in a rat model. J Immunol Res 2014; 2014: 740549.
• Banan A, Fields JZ, Farhadi A, et al: Activation of delta-isoform of protein kinase C is required for oxidant-induced disruption of both the microtubule cytoskeleton and permeability barrier of intestinal epithelia. J Pharmacol Exp Ther 2002; 303:17-28.
• Dabrowski A, Boguslowicz C, Dabrowska M, et al: Reactive oxygen species activate mitogen-activated protein kinases in pancreatic acinar cells. Pancreas 2000; 21; 376-84.
• Takao A: Oxyhemoglobin as the principal cause of cerebral vasospasm: a holistic view of its actions. Crit Rev Neurosurg 1999; 9: 303-18.
• Nishizawa S, Yamamoto S, Yokoyama T, et al: Dysfunction of nitric oxide induces protein kinase C activation resulting in vasospasm after subarachnoid hemorrhage. Neurol Res 1997;19: 558-62.
• Zhao D, Liu Q, Ji Y. et al. Correlation between nitric oxide and early brain injury after subarachnoid hemorrhage. Int J Neurosci 2015; 125(7): 531–9.
• Stein M, Brokmeier L, Herrmann J. et al. Mean hemoglobin concentration after acute subarachnoid hemorrhage and the relation to outcome, mortality, vasospasm, and brain infarction. J Clin Neurosci 2015; 22(3): 530-4.
• Aladag MA, Turkoz Y, Sahna E, et al: The attenuation of vasospasm by using a SOD mimetic after experimental subarachnoidal haemorrhage in rats. Acta Neurochirurgica 2003; 145: 673-77.
• Kamii H, Kato I, Kinouchi H, et al: Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice overexspressing Cu Zn-superoxide dismutase. Stroke 1999; 30: 867-72,
• Nishizawa S, Yamamoto S, Yokoyama T, et al. Chronological changes of arterial diameter, cGMP, and protein kinase C in the development of vasospasm. Stroke 1995; 26: 1916–21.
• Marton LS, Weir BK, Zhang JH. Tyrosine phosphoyrylation and [Ca 2+ ] I elevation induced by hemosylate in bovine endothelial cells: implications for cerebral vasospasm. Neurol Res 1996; 18: 349–53.
• Sugawa M, Koide T, Naitoh S. et al. Phorbol 12, 13- diacetate-induced contraction of the canine basilar artery: role of protein kinase C. J Cereb Blood Flow Metab 1991; 11: 135-42.
• Nishizawa S, Obara K, Koide M. et al. Attenuation of canine cerebral vasospasm after subarachnoid hemorrhage by protein kinase C inhibitors despite augmented phosphorylation of myosin light chain. J Vasc Res. 2003; 40:169-78.
• Matsui T, Takuwa Y, Johshita H, et al. Possible role of protein kinase C-dependent smooth muscle contraction in the pathogenesis of chronic cerebral vasospasm. J Cereb Blood Flow Metab 1991;11: 143–9.
• Minami N, Tani E, Maeda Y. et al. Effects of inhibitors of protein kinase C and calpain in experimental delayed cerebral vasospasm. J Neurosurg 1992; 76: 111-8.
• Zhang T, Su J, Wang K. et al. Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage. Neurosci Lett 2014; 579: 12-7.
• Wang CX, Xie GB, Zhou CH. et al. Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: possible involvement of TLR4/NF-κB-mediated inflammatory pathway. Brain Res 2015; 1594: 245-55.
• Li B, He Y, Xu L. et al. Progranulin reduced neuronal cell death by activation of sortilin 1 signaling pathways after subarachnoid hemorrhage in rats. Crit Care Med 2015; 43(8): e304-11.
• Shao A, Wu H, Hong Y, et al. Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response: possible involvement of NF-κB Pathway and NLRP3 inflammasome. Mol Neurobiol 2016; 53(5): 3462-76.
• Hao G, Dong Y, Huo R. et al. Rutin inhibits neuroinflammation and provides neuroprotection in an experimental rat model of subarachnoid hemorrhage, possibly through suppressing the RAGE-NF-κB inflammatory signaling pathway. Neurochem Res 2016; 41(6): 1496-504.
• Dong YS, Wang JL, Feng DY. et al. Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int J Med Sci 2014; 11(3): 282-90.
• Li Q, Chen Y, Zhang X, Zuo S, Ge H, Chen Y, Liu X, Zhang JH, Ruan H, Feng H. Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats. J Clin Neurosci 2016; 34: 264-270.
• Zuccarello M, Bonasso CL, Lewis AI, Sperelakis N, Rapoport RM Relaxation of suarachnoid hemorrhage- induced spasm of rabbit basilar artery by the K + channel activator cromakalim. Stroke 1996; 27: 311–6.
• Takai Y, Kishimoto A, Inove M, Nishizuka Y. Studies on a cyclic nucleotide independent protein kinase and its proenzyme in mammalian tissues. Purification and characterisation of an active enzyme from bovine cerebellum, J Biol Chem 1977; 252: 7603–9.
• Ignaro LJ Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res 1989; 65: 1-21.
• Palmer RM, Ferrige AG, Moncada S Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524-9.
• Rapaport RM, Draznin MB, Murad F. Endothelium dependent relaxation in rat aorta may be mediated through phosphorylation. Nature 1983; 306: 174-6. protein
• Nishizawa S, Yokota N, Yokoyama T. et al. Obligatory roles of protein kinase c and nitric oxide in the regulation of cerebral vascular tone: an ımplication of a pathogenesis of vasospasm after subarachnoid haemorrhage. Acta Neurochir (Wien). 1998; 140: 1063- 8.
• Eckly-Michel AE, Le Bec A, Lugnier C. Chelerythrine, a protein kinase C inhibitor, interacts with cyclic nucleotide phosphodiesterases Eur J Pharmacol 1997; 324: 85-8.