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环氧合酶-2/CNPase对海洛因海绵状白质脑病中少突胶质细胞凋亡的作用 被引量:4

Roles of cyclooxygenase 2/2′, 3′-cyclic nucleotide3′ phosphohydrolase in the oligodendrocyte apoptosis in heroin-induced spongiform leucoencephalopathy
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摘要 目的探讨环氧合酶(COX)-2、2′,3′-环腺苷酸-3′-磷酸二酯酶(CNPase)对白质少突胶质细胞凋亡调控及阐明海洛因海绵状白质脑病(HSLE)的发病机制。方法对4例HSLE和5例正常对照的小脑、额叶和胼胝体标本,进行HE染色,KB染色,TUNEL染色,MBP、COX-2、CNPase和半胱氨酸蛋白水解酶(caspase)-3免疫组化染色,分析脱髓鞘的病变,比较TUNEL、caspase-3、COX-2和CNPase阳性细胞率,并进行非参数统计分析。结果HSLE组广泛脱髓鞘改变,髓鞘板层间松解,形成空泡样变。KB染色对照组额叶和小脑的白质/灰质灰度比值明显低于HSLE组(t值分别为26.146和35.001,P=0.000)。在额叶、小脑和胼胝体白质,HSLE组的少突胶质细胞凋亡率高于对照组(Z值分别为2.245,4.273和4.250;P=0.000);COX-2阳性细胞数高于对照组(Z值分别为-4.201,-4.177和-4.211,P=0.01)。在额叶和胼胝体白质,HSLE组CNPase表达较对照减少(Z值分别为-2.315和-2.578,P值分别为0.021和0.010)。caspase-3的表达与COX-2呈正相关(Pearson相关系数r=0.858,P=0.003),与CNPase呈负相关(Pearson相关系数r=-0.802,P=0.009)。结论HSLE病变区存在广泛脱髓鞘改变,少突胶质细胞凋亡是HSLE的发病原因之一。COX-2/CNPase表达的改变可能参与少突胶质细胞凋亡。 Objective To investigate the regulation of cyclooxygenase (Cox)-2/2′, 3′-cyclic nucleotide3′ phosphohydrolase (CNPase) on the oligodendrocyte apoptosis in the pathogenesis of the heroininduced spongiform leucoencephalopathy ( HSLE ). Methods Samples of frontal lobe, cerebellum, and corpus callosum were obtained from the brains during autopsy of 4 HSLE patients and 5 patients who died of diseases other than cerebral diseases ( controls ) and underwent light microscopy and electron microscopy. lmmunocytochemistry was carried out to detect the expression of myelin basic protein (MBP) , caspase-3, COX-2, and CNPase protein. Apoptosis was examined by TUNEL staining. Results Widespread demyelination was seen in the white matter of the frontal lobe, cerebellum, and corpus callosum of the HSLE cases, most severely in cerebellum. In he HSLE group, the levels of caspase-3 and COX-2 expression were significantly higher, and the level of CNPase was significantly lower than those of the control group ( all P 〈 0.05 ). Conclusion Widespread demyelination in the white matter is a prevailing' pathological change of HSLE. Oligodendrocyte apoptosis is one of the causes of HSLE. The upregulation of COX-2 and down- regulation of CNPase may contribute to the pathogenesis.
出处 《中华医学杂志》 CAS CSCD 北大核心 2008年第25期1742-1745,共4页 National Medical Journal of China
基金 国家自然科学基金资助项目(30570533 30670414) 国家科技部“973”重点基础研究发展计划基金资助项目(2006CB500705),国家科技部“863”项目(060102A4031) 广东省自然科学基金资助项目(020051)
关键词 海洛因 卡纳万病 少突神经胶质 凋亡 2′ 3′-环核苷酸磷酸二酯酶类 环氧合酶-2 Heroin Cnavan disease Oligodendroglia Apoptosis 2′, 3′-cyclic-nucleotidephosphodiesterases Cyclooxygenase 2
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参考文献13

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共引文献39

同被引文献63

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