Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats

陈佳琳; 姚声涛; 陈良勇; 何朝晖; 孙晓川; 唐文渊; 郭宗铎

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Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats

更新时间：2026-01-09

- Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats
- Journal of Army Medical University Vol. 32, Issue 17, Pages: 1847-1850(2010)
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  CLC： R743.35;R742.06;R978.14
- Published：2010
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陈佳琳,姚声涛,陈良勇,何朝晖,孙晓川,唐文渊,郭宗铎.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].陆军军医大学学报(原第三军医大学学报),2010,32(17):1847-1850.

　Chen Jialin,Yao Shengtao,Chen Liangyong,He Zhaohui,Sun Xiaochuan,Tang Wenyuan,Guo Zongduo.Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(17):1847-1850.
陈佳琳,姚声涛,陈良勇,何朝晖,孙晓川,唐文渊,郭宗铎.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].陆军军医大学学报(原第三军医大学学报),2010,32(17):1847-1850. DOI：

　Chen Jialin,Yao Shengtao,Chen Liangyong,He Zhaohui,Sun Xiaochuan,Tang Wenyuan,Guo Zongduo.Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(17):1847-1850. DOI：

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（P0.01），米诺环素组正常神经元数量（125.73±24.67）个较SAH组明显增加（P0.01）。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，P0.01]；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（P0.01）]。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（P0.01）；米诺环素组MMP-9活性（148.96±6.02）%较SAH组明显降低（P0.01）。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（P0.01）；米诺环素组凋亡阳性细胞数（91.17±7.78）个较SAH组明显下降（P0.01）。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

P0.01). The number of normal neurons was significantly greater in minocycline group (125.73±24.67) than in SAH group (P0.01). 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 (P0.01). The expression level of total MMP-9 was lower in minocycline group (148.96±6.02) than in SAH group (P0.01). 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 (P0.01) and lower in minocycline group than in SAH group (P0.01). 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 (P0.01)

which was then gradually decreased to 91.17±7.78 after treatment with minocycline (P0.01).　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.

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