中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2014年
12期
2254-2258
,共5页
王新施%曾庆意%朱振国%朱攀%徐惠琴%郑荣远
王新施%曾慶意%硃振國%硃攀%徐惠琴%鄭榮遠
왕신시%증경의%주진국%주반%서혜금%정영원
咪唑克生%血脑屏障%基质金属蛋白酶9%组织型基质金属蛋白酶抑制物1%实验性自身免疫性脑脊髓炎
咪唑剋生%血腦屏障%基質金屬蛋白酶9%組織型基質金屬蛋白酶抑製物1%實驗性自身免疫性腦脊髓炎
미서극생%혈뇌병장%기질금속단백매9%조직형기질금속단백매억제물1%실험성자신면역성뇌척수염
Idazoxan%Blood-brain barrier%Matrix metalloproteinases 9%Tissue inhibitor of metalloproteinase 1%Experimental autoimmune encephalomyelitis
目的：观察咪唑克生（ idazoxan，IDA）对小鼠实验性自身免疫性脑脊髓炎（ experimental autoimmune encephalomyelitis， EAE）时血脑屏障（ BBB）通透性及脊髓内的MMP-9／TIMP-1表达的影响。方法：选用36只8周左右的C57BL／6小鼠，随机分为空白对照组、EAE组和IDA干预组，每组12只，采用髓鞘少突胶质细胞糖蛋白35-55（ MOG35-55）诱导经典EAE模型，干预组采用IDA 2 mg／kg腹腔注射，每天2次，共15 d。观察每组大鼠发病情况并进行神经功能障碍评分，采用HE染色和LFB髓鞘染色观察病理改变，采用伊文思蓝荧光定量方法检测BBB通透性的变化，并用Western blotting法检测MMP-9和TIMP-1的表达。结果：空白对照组无一发病，与EAE组比较， IDA干预组神经功能障碍评分明显下降，炎性病灶明显减少，BBB通透性明显降低，MMP-9的表达和MMP-9／TIMP-1比值明显下降，差异有统计学意义（P＜0.05）。结论：IDA可能通过下调MMP-9，降低MMP-9／TIMP-1比值，减轻血脑屏障的降解破坏，从而稳固BBB，降低BBB通透性，减缓小鼠EAE的发病。
目的：觀察咪唑剋生（ idazoxan，IDA）對小鼠實驗性自身免疫性腦脊髓炎（ experimental autoimmune encephalomyelitis， EAE）時血腦屏障（ BBB）通透性及脊髓內的MMP-9／TIMP-1錶達的影響。方法：選用36隻8週左右的C57BL／6小鼠，隨機分為空白對照組、EAE組和IDA榦預組，每組12隻，採用髓鞘少突膠質細胞糖蛋白35-55（ MOG35-55）誘導經典EAE模型，榦預組採用IDA 2 mg／kg腹腔註射，每天2次，共15 d。觀察每組大鼠髮病情況併進行神經功能障礙評分，採用HE染色和LFB髓鞘染色觀察病理改變，採用伊文思藍熒光定量方法檢測BBB通透性的變化，併用Western blotting法檢測MMP-9和TIMP-1的錶達。結果：空白對照組無一髮病，與EAE組比較， IDA榦預組神經功能障礙評分明顯下降，炎性病竈明顯減少，BBB通透性明顯降低，MMP-9的錶達和MMP-9／TIMP-1比值明顯下降，差異有統計學意義（P＜0.05）。結論：IDA可能通過下調MMP-9，降低MMP-9／TIMP-1比值，減輕血腦屏障的降解破壞，從而穩固BBB，降低BBB通透性，減緩小鼠EAE的髮病。
목적：관찰미서극생（ idazoxan，IDA）대소서실험성자신면역성뇌척수염（ experimental autoimmune encephalomyelitis， EAE）시혈뇌병장（ BBB）통투성급척수내적MMP-9／TIMP-1표체적영향。방법：선용36지8주좌우적C57BL／6소서，수궤분위공백대조조、EAE조화IDA간예조，매조12지，채용수초소돌효질세포당단백35-55（ MOG35-55）유도경전EAE모형，간예조채용IDA 2 mg／kg복강주사，매천2차，공15 d。관찰매조대서발병정황병진행신경공능장애평분，채용HE염색화LFB수초염색관찰병리개변，채용이문사람형광정량방법검측BBB통투성적변화，병용Western blotting법검측MMP-9화TIMP-1적표체。결과：공백대조조무일발병，여EAE조비교， IDA간예조신경공능장애평분명현하강，염성병조명현감소，BBB통투성명현강저，MMP-9적표체화MMP-9／TIMP-1비치명현하강，차이유통계학의의（P＜0.05）。결론：IDA가능통과하조MMP-9，강저MMP-9／TIMP-1비치，감경혈뇌병장적강해파배，종이은고BBB，강저BBB통투성，감완소서EAE적발병。
[ ABSTRACT] AIM:To study the effect of idazoxan ( IDA) on the permeability of blood-brain barrier ( BBB) and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in mouse ex-perimental autoimmune encephalomyelitis (EAE).METHODS: Female C57BL/6 mice (n=36) were randomly divided into control group, EAE group and IDA group, with 12 mice in each group.EAE was induced by myelin oligodendrocyte glycoprotein 35-55 ( MOG35-55 ) .IDA (2 mg/kg, ip, bid) was administered for 15 d after immunization.The neurological defects of the mice were observed daily and scored.The pathological changes were observed under microscope with HE stai-ning and LFB myelin staining.The BBB permeability was detected by Evans blue extravasation.The expression of MMP-9 and TIMP-1 in the brain of EAE mice was determined by Western blotting.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the inflammation was relieved, the BBB permeability was re-duced, and the expression MMP-9 and the ratio of MMP-9/TIMP-1 were decreased ( P<0.05 ) .CONCLUSION: The neuroprotective effect of IDA on mouse EAE might be related to the down-regulation of MMP-9 and the ratio of MMP-9/TIMP-1, thus reducing the degradation of BBB and the permeability of BBB, and ameliorating the pathologic process of EAE.
