米诺环素对大鼠脑出血损伤的保护作用及对Bcl-2和MMP-9表达的影响  

Action of Minocycline on Brain Injury after Intracerebral Hemorrhage and Protective Effects on the Expression of Bcl-2 and Matrix Metalloproteinase-9

作　　者：秦志华[1] 刘锐[2] 

机构地区：[1]天津医学高等专科学校药理学教研室,天津300222 [2]天津天士力集团研究院,天津300410

出　　处：《中国药学杂志》2011年第6期430-433,共4页Chinese Pharmaceutical Journal

摘　　要：目的观察B细胞淋巴瘤/白血病-2(Bcl-2)和基质金属蛋白酶-9(MMP-9)在大鼠脑出血后脑损伤机制中的作用及米诺环素(minocycline)对脑损伤的保护作用。方法 Wistar大鼠随机分为3组:假手术组(Sham)、模型组(Model)及米诺环素组(Minocycline),每组又按时间点不同分为6,12 h,1,2,3,5,7 d亚组。根据大鼠脑立体定位术,制备大鼠脑内囊出血模型。采用神经系统功能评分和体感诱发电位对脑出血模型进行评价。并于不同时间点开颅取脑组织对针眼前脑组织进行含水量的测定,针眼后脑组织制成病理切片,苏木精-伊红染色法用于脑组织形态学的观察,免疫组化染色用于检测出血周围脑组织Bcl-2和MMP-9蛋白的表达情况。结果大鼠内囊出血模型制备成功。免疫组化结果表明,与假手术组相比,模型组各时间点出血周围脑组织的Bcl-2和MMP-9蛋白表达增加(P<0.001),脑组织含水量增加(P<0.001);与模型组相比,米诺环素组各时间点出血周围脑组织Bcl-2表达明显增加,MMP-9表达明显下降,脑组织含水量明显下降。结论米诺环素对脑出血后脑损伤有保护作用,可能与Bcl-2表达增加以及MMP-9表达减少有关。OBJECTIVE To observe the action of Bcl-2 and MMP-9 in the mechanism of brain injury after intracerebral hemorrhage in rats and the protection of minocycline on the brain damage. METHODS The experiment was divided into three groups （Sham group, Model group, Minocycline group） , then all groups were divided into seven subgroups according treatment time separate- ly （6, 12 h, 1,2,3,5,7 d）, we established the model of intracerebral hemorrhage in light of the stereotactic method, then evaluated it with the nervous symptoms and somatosensory evoked potentials. At different time, brain tissue was taken out of the skull, fixed and divided into two parts, one part in front of the needle was used to determine the brain water content, and the other part after the needle was used to detect morphological observation with hematoxylin-eosin staining and the expressions of Bcl-2 and MMP-9 with immunohis- tochemistry separately. RESULTS We made the model of intracerebral hemorrhage successfully, compared with the Sham group, ex- pression of Bcl-2 and MMP-9 of Model group at all time increased （ P 〈 0. 001 ）, the brain water content increased （ P 〈 0. 001 ）. Com- pared with the model group, expression of Bcl-2 of minocycline group increased significantly, MMP-9 decreased significantly. The brain water content decrease significantly. CONCLUSION Minocycline has the protection on the brain injury after intracerebral hemorrhage, which may be related to the increase of Bcl-2 and the decrease of MMP-9.

关 键 词：脑出血 B细胞淋巴瘤/白血病-2 基质金属蛋白酶-9 米诺环素 

分 类 号：R965[医药卫生—药理学]