[1]陈佳琳,姚声涛,陈良勇,等.米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].第三军医大学学报,2010,32(17):1847-1850.
 Chen Jialin,Yao Shengtao,Chen Liangyong,et al.Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J].J Third Mil Med Univ,2010,32(17):1847-1850.
点击复制

米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
32卷
期数:
2010年第17期
页码:
1847-1850
栏目:
论著
出版日期:
2010-09-15

文章信息/Info

Title:
Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats
作者:
陈佳琳姚声涛陈良勇何朝晖孙晓川唐文渊郭宗铎
贵州省遵义医院:儿科,神经外科;重庆医科大学附属第一医院神经外科
Author(s):
Chen JialinYao ShengtaoChen LiangyongHe ZhaohuiSun XiaochuanTang WenyuanGuo Zongduo
Department of Neurosurgery, Department of Pediatrics, Zunyi Hospital, Zunyi, Guizhou Province, 563002; Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
关键词:
米诺环素基质金属蛋白酶-9蛛网膜下腔出血早期脑损伤
Keywords:
minocyclinematrix metalloproteinase 9subarachnoid hemorrhageearly brain injury
分类号:
R743.35; R742.06; R978.14
文献标志码:
A
摘要:
目的    探讨米诺环素对大鼠蛛网膜下腔出血(subarachnoid hemorrhage, SAH)后早期脑损伤(early brain injury, EBI)的保护作用及其机制。    方法      健康4月龄雄性SD大鼠48只,体质量250~300 g,按随机数字表法分为假手术组(sham组)、SAH组、安慰剂组(vehicle 组)和米诺环素组(minocycline组),每组各12只。采用经视交叉前池注血法建立蛛网膜下腔出血模型。各组于处理后24 h经HE染色观察海马CA1区神经元形态;运用Western blot和明胶酶谱方法检测大鼠海马基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达;采用原位末端标记法(TUNEL)检测海马神经元凋亡。    结果      HE染色显示:SAH组大鼠海马CA1正常神经元数量(67.42±20.35)个较sham组(145.5±21.23)个明显下降(P<0.01),米诺环素组正常神经元数量(125.73±24.67)个较SAH组明显增加(P<0.01)。Western blot检测结果显示:sham组大鼠海马MMP-9蛋白表达水平较低(1.94±0.39)%,SAH后24 h MMP-9表达明显增高[(103.60±7.72)%,与sham组相比明显升高,P<0.01];米诺环素组MMP-9蛋白表达明显降低[(74.52±6.47)%,较SAH组明显降低(P<0.01)]。明胶酶谱检测显示:sham组大鼠海马未检测到活性[(0.39±0.23)%]、SAH组MMP-9活性(201.81±6.31)%较Sham组明显增高(P<0.01);米诺环素组MMP-9活性(148.96±6.02)%较SAH组明显降低(P<0.01)。TUNEL检测显示:sham组海马神经元未检测到TUNEL阳性细胞,SAH后24 h 海马TUNEL阳性细胞数明显增加[(192.17±6.31)个],与sham组相比差异有统计学意义(P<0.01);米诺环素组凋亡阳性细胞数(91.17±7.78)个较SAH组明显下降(P<0.01)。    结论      大鼠蛛网膜下腔出血后,米诺环素能够改善大鼠海马神经元形态,对早期脑损伤发挥保护作用;其机制可能与米诺环素抑制MMP-9活性及其蛋白表达,减轻海马神经元凋亡有关。
Abstract:
Objective To study the effect of minocycline on early brain injury (EBI) after subarachnoid hemorrhage (SAH) and its mechanism. Methods Forty-eight adult male SD rats were randomly divided into sham operation group, SAH group, vehicle group and minocycline group. A SAH model was induced by injecting autologous arterial blood into the prechiasmatic cistern. Morphology of CA1 region in hippocampus of rats was observed with hematoxylin and eosin (HE) staining in each group. Expression of MMP-9 in hippocampus was detected at 24 h by Western blotting and zymography. Neuronal apoptosis in hippocampus was determined by TUNEL. Results HE staining showed that the number of normal neurons in CA1 region of hippocampus was significantly lower in SAH group than in sham operation group (67.42±20.35 vs 145.5±21.23, P<0.01). The number of normal neurons was significantly greater in minocycline group (125.73±24.67) than in SAH group (P<0.01). Western blotting showed that the expression level of total MMP-9 was lower in minocycline group (1.94±0.39) and significantly higher in SAH group (103.60±7.72) at 24 h than in sham operation group (P<0.01). The expression level of total MMP-9 was lower in minocycline group (148.96±6.02) than in SAH group (P<0.01). The zymography showed that the expression level of active MMP-9 could not be measured in sham group, which was significantly higher in SAH group than in sham operation group (P<0.01) and lower in minocycline group than in SAH group (P<0.01). TUNEL showed no positive neurons in sham operation group, and the number of positive neurons was greater at 24 h in SAH group (192.17±6.31) than in sham operation group (P<0.01), which was then gradually decreased to 91.17±7.78 after treatment with minocycline (P<0.01). Conclusion Minocycline can improve the morphology of neurons in hippocampus and EBI after SAH by inhibiting the expression of total and active MMP-9 and decreasing the neuronal apoptosis in hippocampus.

参考文献/References:

陈佳琳, 姚声涛, 陈良勇, 等. 米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].第三军医大学学报,2010,32(17):1847-1850.

相似文献/References:

[1]李明,孙守兵,周越,等.去甲肾上腺素诱导人巨噬细胞MMP-9的表达及机制[J].第三军医大学学报,2012,34(17):1758.
 Li Ming,Sun Shoubing,Zhou Yue,et al.Norepinephrine induces expression of matrix metalloproteinase-9 in human macrophages and its mechanisms[J].J Third Mil Med Univ,2012,34(17):1758.
[2]徐兴华,孙文娟,周岐新,等.氨氯地平对人乳腺癌细胞株MDA-MB-231侵袭影响的体外实验[J].第三军医大学学报,2008,30(04):340.
 XU Xing-hua,SUN Wen-juan,ZHOU Qi-xin,et al.Amlodipine inhibits in vitro invasion of human breast carcinoma cells MDA-MB-231[J].J Third Mil Med Univ,2008,30(17):340.
[3]李金平,程军,田卓,等.南蛇藤素对ApoE基因敲除小鼠主动脉壁MIF及MMP-9表达的影响[J].第三军医大学学报,2008,30(09):827.
 LI Jin-ping,CHENG Jun,TIAN Zhuo,et al.Celastrol down-regulates expressions of MIF and MMP-9 in the aorta of ApoE gene knockout mice[J].J Third Mil Med Univ,2008,30(17):827.
[4]梁成,晏红,施鑫鹤,等.缺血再灌注期实施亚低温与再建血运治疗时间窗的影响[J].第三军医大学学报,2011,33(18):1956.
 Liang Cheng,Yan Hong,Shi Xinhe,et al.Effect of sub-hypothermia during ischemia reperfusion on time window for restoration of blood flow in rats[J].J Third Mil Med Univ,2011,33(17):1956.
[5]傅勇,胡华梅,谭益,等.基质金属蛋白酶-9基因多态性与食管鳞状细胞癌易感性的关联研究[J].第三军医大学学报,2009,31(12):1131.
 FU Yong,HU Hua-mei,TAN Yi,et al.Correlation between the polymorphism of matrix metalloproteinase-9 and esophageal squamous cell carcinoma patients in Southwest China[J].J Third Mil Med Univ,2009,31(17):1131.
[6]秦蓁,罗彬,王旭东.肺癌MMP-9表达与血管生成的关系及其意义[J].第三军医大学学报,2009,31(07):595.
 QIN Zhen,LUO Bin,WANG Xu-dong.Relationship of matrix metalloproteinase-9 expression and angiogenesis in lung carcinoma and its significance[J].J Third Mil Med Univ,2009,31(17):595.
[7]蒋国会,李鱼,李光勤.抑制基质金属蛋白酶-9对尿激酶溶栓出血性转化的干预效果[J].第三军医大学学报,2008,30(21):1971.
[8]李莹,宋耀明,黄岚,等.培哚普利与坎地沙坦对慢性心力衰竭患者ET-1、IL-6、MMP-9及左心室重塑的影响[J].第三军医大学学报,2011,33(06):633.
 Li Ying,Song Yaoming,Huang Lan,et al.Effects of perindopril and candesartan on left ventricular remodeling and serum ET-1, IL-6 and MMP-9 levels in patients with chronic heart failure[J].J Third Mil Med Univ,2011,33(17):633.
[9]唐兆华,廖正步,谢延风,等.氧糖剥夺、复氧后损伤星形胶质细胞中MMP-9的表达变化与意义[J].第三军医大学学报,2012,34(05):387.
 Tang Zhaohua,Liao Zhengbu,Xie Yanfeng,et al.Significance of MMP-9 expression in astrocytes after oxygen-glucose deprivation/reoxygenation in vitro[J].J Third Mil Med Univ,2012,34(17):387.
[10]张娟,陈旻静,王大伟,等.组织蛋白酶D和基质金属蛋白酶-9在皮肤恶性黑色素瘤中的表达[J].第三军医大学学报,2012,34(10):1002.
 Zhang Juan,Chen Minjing,Wang Dawei,et al.Expression of Cath-D and MMP-9 in cutaneous malignant melanoma[J].J Third Mil Med Univ,2012,34(17):1002.

更新日期/Last Update: 2010-09-09