CAJ | 학술논문

目的通过观察大鼠蛛网膜下腔出D-（SAH）后早期脑皮层紧密连接相关蛋白Claudin－5、ZO－1表达的变化及JNK抑制剂SP600125对其表达的影响，探讨SAH后早期脑损伤的机制。方法成年雄性SD大鼠75只，随机分成假手术组（sham组）、SAH组、SAH＋DMSO组、SAH＋sP600125（10mg／kg）组和sAH＋sP600125（30mg／kg）组5组。采用血管内穿刺法建立大鼠SAH模型，在SAH后24h时，应用电镜观察各组脑皮层微血管血脑屏障形态学变化；应用Western blot检测各组中脑皮层Claudin－5、ZO－1表达的变化。结果SAH后早期脑皮层微血管发生明显损伤改变；与sham组相比，SAH组出血后24hClaudin－5、ZO－1的表达水平明显降低（P〈0．05），c-Jun氨基端激酶（JNK）抑制剂SP600125明显改善了脑皮层微血管形态学损伤程度，并抑制了Claudin－5、ZO－1表达水平的降低。结论大鼠SAH后早期血脑屏障结构破坏是早期脑损伤关键性机制之一；SP600125可能通过抑制细胞凋亡、保护血脑屏障发挥SAH早期脑损伤的神经保护作用。
목적통과관찰대서주망막하강출D-（SAH）후조기뇌피층긴밀련접상관단백Claudin－5、ZO－1표체적변화급JNK억제제SP600125대기표체적영향，탐토SAH후조기뇌손상적궤제。방법성년웅성SD대서75지，수궤분성가수술조（sham조）、SAH조、SAH＋DMSO조、SAH＋sP600125（10mg／kg）조화sAH＋sP600125（30mg／kg）조5조。채용혈관내천자법건립대서SAH모형，재SAH후24h시，응용전경관찰각조뇌피층미혈관혈뇌병장형태학변화；응용Western blot검측각조중뇌피층Claudin－5、ZO－1표체적변화。결과SAH후조기뇌피층미혈관발생명현손상개변；여sham조상비，SAH조출혈후24hClaudin－5、ZO－1적표체수평명현강저（P〈0．05），c-Jun안기단격매（JNK）억제제SP600125명현개선료뇌피층미혈관형태학손상정도，병억제료Claudin－5、ZO－1표체수평적강저。결론대서SAH후조기혈뇌병장결구파배시조기뇌손상관건성궤제지일；SP600125가능통과억제세포조망、보호혈뇌병장발휘SAH조기뇌손상적신경보호작용。
Objective Aimed to clarify the molecular mechanism after subarachnoid hemorrhage （SAH） by investigating the expression of tight junction protein Claudin-5 and ZO-1 and the effects of SP600125 on them. Methods Seventy-five male Sprague Dawley rats （300 to 350 g） were randomly divided into sham,SAH,SAH ＋ DMSO （dimethyl sufoxide） solution,SAH ＋SP600125 （C-Jun N-terminal kinase inhibitor）10 mg/kg,and SAH ＋SP600125 30 mg/kg groups. The standard endovaseular perforation was performed to produce experimental SAH. The JNK inhibitor SP600125 was intraperitoneally administered at 1 hour before and 6 hours after SAH. Results At 24 hours after SAH,signs of microvessels injury were observed in brain cortex. Compared with the sham group,expression of Claudin-5 and ZO-1 was sig- nificantly decreased （P 〈 0.05 ）. JNK inhibitior SP600125 suppressed the decrease of Claudin-5 and ZO-1 expression, attenuated blood-brain barrier disruption in rats after SAH. Conclusions The blood-brain barrier disruption is an important mechanism of early brain injury after SAH. JNK inhibitor SP600125 improves neurological outcomes and provides neuropmtecfion against acute events after SAH such as bloodbrain barrier disruption and cell apoptosis.