【目的】 探讨血红素加氧酶(heme oxygenase,HO)与细胞红蛋白(cytoglobin,CYGB)表达的关系,为缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)的防治提供实验依据。 【方法】 将7日龄新生SD大鼠170只随机分为正常对照组、假手术组、HIBD组、HIBD+Hemin组、HIBD+ZnPP组5组。其中HIBD组、HIBD+Hemin组及HIBD+ZnPP组在HIBD模型制备前12 h,分别腹腔注射生理盐水、Hemin及ZnPP,然后制备HIBD模型。术后于0、24、48 h采用免疫组化染色法分析HO -1及CYGB蛋白表达特点。 【结果】 缺氧后HO -1及CYGB表达随时间增长而递增,而且对于同一时间点HIBD+Hemin组HO -1及CYGB的表达均明显高于HIBD+ZnPP组,HIBD组居中,各组间比较差异有统计学意义;5组海马HO -1及CYGB表达均高度相关,0 h的r为0.687~0.916、24 h的r为0.473~0.903、48 h的r为0.659~0.962,皮质两者的表达亦有相同结果。 【结论】 Hemin诱导HO-1能使CYGB高表达,而ZnPP抑制HO-1则使CYGB表达减少;HO -1及CYGB的表达在HIBD时存在极明显的正相关性;实验证明脑缺氧缺血损伤时HO -1对CYGB的表达可能具有一定的正性调控作用。
Abstract
【Objective】 To discuss the relation between the protein expression of heme oxygenase-1(HO-1) and cytoglobin (CYGB),and whether hemin would reduce the brain damage against hypoxic-ischemic damage. 【Methods】 SD rats of 7-day old were divided into 5 groups randomly,including control group,sham-operated group,HIBD group,HIBD +Hemin group,and HIBD+ZnPP group.The rats of HIBD+Hemin group,HIBD group and HIBD+ZnPP group were given Hemin,normal saline or ZnPP 12 hours before the operation.The rats of three last groups were made for HIBD model.All the groups were killed at 0 h,24 h,48 h after HIBD.At 0 h,24 h,48 h after hypoxic-ischemic,observed the protein expression of HO-1 and CYGB in the brain. 【Results】 The protein expression of HO-1 and CYGB in all HIBD model groups were increased as time gone on.At any time after hypoxic-ischemic brain damage the expression of HO-1 and CYGB in the HIBD model groups were more than those in sham-operated group and control group.And in three HIBD model groups the expression of HO-1 and CYGB were showed by immunohistochemistry:HIBD+Hemin group>HIBD group>HIBD+ZnPP group,comparison of the three groups was with significant difference.The expression of HO-1 and CYGB had positive correlations in contex and hipppcampi in five groups.The relative factors r at 0h after HIBD were 0.687~0.916,24 h after HIBD were 0.473~0.903,48 h after were 0.659~0.962.The contex also had similar result. 【Conclusions】 Hemin which was the abduction of HO-1 could increase the expression of HO-1 in contex and hippocampus of HIBD+Hemin group.ZnPP which was the depressor of HO could decrease the expression of HO-1 of the HIBD+ZnPP group.The expression of HO-1 and CYGB was consistency,and they may have clear positive correlation.
关键词
细胞红蛋白 /
血红素加氧酶 /
缺氧缺血性脑损伤 /
表达关系
Key words
cytoglobin /
heme oxygenase-1 /
hypoxic-ischemic brain damage /
relation
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Schmidt M,Gerlach F,Avivi A,et al.Cytoglobin is a respiratory protein in connective tissue and neurons,which is up-regulated by hypoxia[J].J Biol Chem,2004,279:8063-8069.
[2] Fordel E,Geuens E,Dewilde S,et al.Cytoglobin expression is up regulated in all tissues upon hypoxia: an in vitro and in vivo study by quantitative real-time PCR[J].Biochem Biophys Res Commun,2004,319(2):342-348.
[3] 郑淮武,史雪川,庄静文,等.缺氧缺血性脑损伤新生大鼠脑组织细胞红蛋白的表达[J].中华围产医学杂志,2010,3(1):37-40.
[4] 黄缄,高文祥,廖卫公,等.培养心肌细胞缺氧时胞红蛋白表达变化特点[J].第三军医大学学报,2006,86 (5):321-324.
[5] Geuens E,Brouns I,Flamez D,et al.A globin in the nucleus？[J].J Biol Chem,2003,278(33):30417-30420.
[6] Dwyer BE,Lu SY,Laitinen JT,et al.Protective properties of tin-and manganese-centered porphyrins against hydrogen peroxide-mediated injury in rat astroglial cells[J].J Neurochem,1998,71(6):2497-2504.
[7] Morisaki H,Katayama T,Kotake Y,et al.Carbon monoxide modulates endotoxin induced microvascular leukocyte adhesion through platelet dependent mechanisms[J].J Anesthesiology,2002,97(3):701-709.
[8] Kadoya C,Domino EF,Yang GY,et al.Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats[J].Stroke,1995,26(6):1035-1038.
[9] Mancuso C,Perluigi M,Cini C,et al.Heme oxygenase and cyclooxygenase in the central nervous system:A functional interplay[J].J Neurosci Res,2006,84(7):1385-1391.
[10] Brann DW,Bhat GK,Lamar CA,et al.Gaseous transmitters and neuroendocrine regulation[J].Neuroendocrinology,1997,65(6):385-395.
[11] Fordel E,Geuens E,Dewilde S,et al.Cytoglobin expression is up regulated in all tissues upon hypoxia: an in vitro and in vivo study by quantitative real-time PCR[J].Biochem Biophys Res Commun,2004,319(2):342-348.
[12] 毕建立,江朝光,周乃康.血红素氧合酶的抗损伤机制[J].中国体外循环杂志,2005,3(2):123-124.
[13] Rodgers KR.Heme-based sensors in biological systems[J].Curr Opin Chem Biol,1999,3(2):158-167.
基金
广东省科技计划项目(2008B680701036);广东省科技计划项目(B2009180)
PDF(567 KB)
