Effect of SB203580 on cell apoptosis during lung ischemic/reperfusion injury in rats

Abstract

Abstract: AIM: To explore the effect of SB203580, P38 mitogen activated protein kinase specific inhibitor(p38MAPK), on apoptosis during lung ischemic/reperfusion injury in rats. METHODS: 30 rats were randomly divided into three groups, group control (Group C ), group lung ischemia/reperfusion injury (Group I/R) and group SB203580 (Group S).The changes of arteriae pulmonalis apoptosis were detected with TdT-mediated dUTP nick end labeling (TUNEL). The content of Bcl-2 and Bax in cytoplasm were determined with immunohistochemistry and meanwhile the ultrastruction changes of lung were observed under electron microscope. RESULTS: Compared with Group C, the expressions of Bcl-2, Bax protein were increased and the ratio of Bcl-2/Bax were decreased in Group I/R (all P <0.01), and the apoptosis index(AI) was increased, the abnormal changes of the lung tissue in morphologically were significant in Group I/R.After using SB203580, the expression of Bcl-2 protein was increased and the expression of Bax protein was decreased, the ratio of Bcl-2/Bax was increased(all P < 0.01), the values of AI was decreased in Group I/R, and the abnormal changes of the lung tissue in morphologically were lessen at different degree (all P < 0.01). CONCLUSION: SB203580 produces notable protective effects on lung ischemic/reperfusion injury in rats by up-regulating Bcl-2 protein expression, downregulating Bax protein expression in lung tissue and regulating the balance of Bcl-2 protein and Bax protein, decreasing apoptosis.

Key words: lung, reperfusion injury, SB203580, p38 mitogen activated protein kinase, apoptosisun

CLC Number:

R363

ZHENG Yan-rong, SHI Lu, HONG Jia-lin, JIA Xu-guang, WANG Wan-tie. Effect of SB203580 on cell apoptosis during lung ischemic/reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(11): 1242-1246.

References

[1] Sekido N, Mukadia N, Harada A, et al.Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8[J].Nature, 1993, 365(10):654.
[2] Ito T.p38MAP klnae is requied for vasopressin-stimulated HSP27 induction in Aortis smooth muscle cells[J].Hepertenslon, 2002, 35(2):673-683.
[3] 段红, 李源王鲜平, 等.川芎嗪对缺血再灌注大鼠心肌细胞凋亡的影响[J].武警医学, 2000, 11(2):70-73.
[4] Ng CS, Wan S, Yin AP.Pulmonary ischaemia-reperfusion injury:role of apoptosis[J].Eur Repair J, 2005, 25(2): 356-363.
[5] Fischer S, Maclean AA, Liu M, et al.Dynamic changes in apoptotic and necrotic cell death correlate with severity of ishchemia-reperfusion injury in lung transplantation[J]. Am J Respir Crit Care Med, 2000, 162(5):1932-1939.
[6] 戴雍月, 徐正衤介, 王万铁, 等.细胞凋亡和Bcl-2、Bax 基因在兔肺缺血再灌注损伤中的作用[J].温州医学院学报, 2006, 36(1):26-29.
[7] Houpt JB, Mcmillan R, Wein C, et al.Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee[J].J Rheumatol, 1999, 26(11):242-243.
[8] Michel BA, Stucki G, Frey D, et al.Chondroitins 4 and 6 sulfate in osteoarthritis of the knee:a randomized, controlled trial[J].Arthritis Rheum, 2005, 52(3):779-786.
[9] Lazebnik LB, Drozdov VN.Efficacy of chondroitin sulphate in the treatment of elderly patients with gonarthrosis and coxarthrosis[J].Ter Arkh, 2005, 77(8):64-69.
[10] Park KM, Chen A, Bonventre JV, et al.Prevention of kidney ischemia-reperfusion induced functional injury and JNK, P38, and MAPK1 kinase activation by remote ischemia pretreatment[J].J Biol Chem, 2001, 27(3):11870-11876.
[11] 刘志刚, 陈向东.参附对大鼠肠缺血再灌注损伤时 p38 丝裂素活化蛋白激酶信号转导通路的影响[J]. 中国现代医学杂志, 2008, 18(20):2976-2982.
[12] 王雨, 汤礼军, 戴睿武, 等.p38MAPK 信号转导途径对早期缺血再灌注期间离体肝脏ICAM1 mRNA 表达的影响[J].华西医学, 2009, 24(8):2087-2091.
[13] Bonventre JV.Kidney ischemia preconditioning[J].Current Opinion in Nephrology &Hypertension, 2002, 71(1): 43-48.
[14] 孙立倩, 景晓彬, 崔建忠.SB203580 对IR 鼠模型脑组织中神经元凋亡的影响[J].山东医药, 2009, 49(2):34-35.

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