CAJ | 학술논문

目的：研究二甲胺四环素对蛛网膜下腔出血（SAH）后早期脑损伤的保护作用及其机制。方法血管内穿刺法建立SD大鼠SAH模型，将77只SD大鼠随机分为空白对照组（22只）、SAH+溶剂组（28只）、SAH+二甲胺四环素组（27只），术后1h予以腹腔注射二甲胺四环素（135mg/kg）或者等量溶剂，术后24h分别评估各组大鼠死亡率、SAH评分、神经功能评分和脑含水量情况，以Western blot检测Bcl-2和caspase-3蛋白表达，TUNEL染色检测神经细胞凋亡。结果 SAH+溶剂组大鼠死亡率（21.4%）和SAH+二甲胺四环素组死亡率（18.5%）均明显高于空白对照组（均P＜0.05），但前两组间无统计学差异（P＞0.05）。SAH+二甲胺四环素组脑含水量（79.36±0.07）%低于SAH+溶剂组（80.00±0.16）%，组间比较有统计学差异（P＜0.05），两组脑含水量均高于空白对照组（79.13±0.08）%，均有统计学差异（均P＜0.05）。空白对照组Bcl-2蛋白表达为1.00±0.12，caspase-3蛋白表达为1.00±0.21，SAH+溶剂组Bcl-2表达为0.65±0.03，caspase-3表达为1.53±0.24，与空白对照组比较，SAH+溶剂组Bcl-2表达明显降低，caspase-3表达明显升高（均P＜0.05），SAH+二甲胺四环素组Bcl-2表达为0.93±0.13，caspase-3表达为1.11±0.18，与SAH+溶剂组比较均有统计学差异（均P＜0.05）。空白对照组神经细胞TUNEL阳性率（1.75±0.96）%，SAH+溶剂组TUNEL阳性率（31.50±3.70）%，与空白对照组相比，SAH+溶剂组TUNEL阳性率明显增加（P＜0.05）；而SAH+二甲胺四环素组TUNEL阳性率（14.25±2.50）%，明显低于SAH+溶剂组（P＜0.05）。结论二甲胺四环素可明显减轻SAH后的早期脑损伤，可能与其抑制神经细胞凋亡有关。
목적：연구이갑알사배소대주망막하강출혈（SAH）후조기뇌손상적보호작용급기궤제。방법혈관내천자법건립SD대서SAH모형，장77지SD대서수궤분위공백대조조（22지）、SAH+용제조（28지）、SAH+이갑알사배소조（27지），술후1h여이복강주사이갑알사배소（135mg/kg）혹자등량용제，술후24h분별평고각조대서사망솔、SAH평분、신경공능평분화뇌함수량정황，이Western blot검측Bcl-2화caspase-3단백표체，TUNEL염색검측신경세포조망。결과 SAH+용제조대서사망솔（21.4%）화SAH+이갑알사배소조사망솔（18.5%）균명현고우공백대조조（균P＜0.05），단전량조간무통계학차이（P＞0.05）。SAH+이갑알사배소조뇌함수량（79.36±0.07）%저우SAH+용제조（80.00±0.16）%，조간비교유통계학차이（P＜0.05），량조뇌함수량균고우공백대조조（79.13±0.08）%，균유통계학차이（균P＜0.05）。공백대조조Bcl-2단백표체위1.00±0.12，caspase-3단백표체위1.00±0.21，SAH+용제조Bcl-2표체위0.65±0.03，caspase-3표체위1.53±0.24，여공백대조조비교，SAH+용제조Bcl-2표체명현강저，caspase-3표체명현승고（균P＜0.05），SAH+이갑알사배소조Bcl-2표체위0.93±0.13，caspase-3표체위1.11±0.18，여SAH+용제조비교균유통계학차이（균P＜0.05）。공백대조조신경세포TUNEL양성솔（1.75±0.96）%，SAH+용제조TUNEL양성솔（31.50±3.70）%，여공백대조조상비，SAH+용제조TUNEL양성솔명현증가（P＜0.05）；이SAH+이갑알사배소조TUNEL양성솔（14.25±2.50）%，명현저우SAH+용제조（P＜0.05）。결론이갑알사배소가명현감경SAH후적조기뇌손상，가능여기억제신경세포조망유관。
Objective To investigate the effect of minocycline on early brain injury (EBI) fol owing subarachnoid hem-orrhage (SAH) in rats. Methods SAH was induced by the filament perforation model in male Sprague Dawley rats. SD rats (n=77) were randomly assigned to sham (n=22), SAH+vehicle (n=28), and SAH+minocycline (n=27) groups. Minocycline (135 mg/kg) or equal volume of vehicle was administered 1 h after SAH induction. Mortality, neurological scores, brain edema were e-valuated 24 h after SAH. Cel apoptosis were examined by TUNEL staining, and the expression of caspase- 3 and Bcl- 2 was as-sayed by Western blot at the same time point. Results The mortality was 21.4% in SAH+vehicle group, 18.5% in the SAH+minocycline group, while no death was observed in sham- operated rats;there was no significant difference in mortality be-tween SAH+vehicle and SAH+minocycline groups (P>0.05), but the mortality in these two groups was much higher than that in sham group(P<0.05). The water content of brain was significantly increased in the SAH+vehicle group (80.00±0.16)%compared with that in sham group [(79.13±0.08)%, P<0.05]. Minocycline treatment markedly reduced brain water content (79.36±0.07)%compared with that in SAH+vehicle group (P<0.05). Caspase- 3 levels were markedly increased in SAH+vehicle group (1.53± 0.24) compared with sham group (1.00 ±0.21). Minocycline treatment significantly reduced caspase- 3 levels, compared to SAH+vehicle group (1.11 ±0.18, P<0.05). A significant decrease in Bcl- 2 expression was observed in SAH+vehicle group (0.65 ±0.03) compared with the sham group (1.00 ±0.12). The treatment of minocycline upregulated the expression of Bcl- 2, compared to SAH+vehicle group (0.93±0.13, P<0.05). TUNEL- positive cel s were increased in the cortex of SAH+vehicle rats, compared to sham group [(31.50±3.70)%, P<0.05]. Minocycline treatment significantly reduced the number of TUNEL positive cel s, compared to SAH+vehicle group [(14.25±2.50)%, P<0.05]. Conclusion Minocycline may reduce early brain injury after subarachnoid hemorrhage in rats by inhibiting cel apoptosis, which is associated with down- regulation of caspase- 3 and up- regulation of Bcl- 2.