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目的:脑梗死后星形胶质细胞的过度活化将形成胶质瘢痕阻碍轴突生长,基质金属蛋白酶(ma- trix metalloproteinases,MMPs)是分解细胞外基质的蛋白酶类中最重要的一类。本实验拟研究滋补肝肾中药复健片对局灶性脑缺血大鼠脑内MMP-2、MMP-9表达的影响,探讨复健片治疗缺血性卒中的作用机理。方法:雄性Wistar大鼠49只随机分为假手术组、模型组(分设1w、2w、3w组)、给药组(分设1w、2w、3w组),模型组与给药组进行右侧近端大脑中动脉电凝术造成大鼠局灶性脑缺血模型,假手术组行同样开颅术,但不凝闭大脑中动脉,其余操作同模型组。于造模成功后第6天起药物组灌胃给予复健片,剂量为9g生药/kg/d,余二组分别灌胃给予同等量生理盐水,日1次。分别在相应时间点取材后用酶联免疫吸附法检测MCAO大鼠脑内MMP-2、MMP-9的表达。结果:模型组MMP-2、MMP-9活性在给药1周后较假手术组有显著差异,说明造模成功;模型组在给药1周、2周和3周后无差异;药物组在治疗2周和3周后同组间较前期有差异,说明MMP-2、MMP-9活性随着用药时间的延长逐渐表达增强;药物组在治疗1周后MMP-2、MMP-9活性较同期模型组尚无显著差异,但2周及3周后表达显著增强,与同期的模型组产生了显著差异。结论:复健片治疗缺血性卒中的作用机理可能与后期上调MMP-2、MMP-9的表达,从而抑制胶质瘢痕的形成,以解除神经功能重塑的负面因素有关。
OBJECTIVE: Over-activation of astrocytes after cerebral infarction will cause glial scars to block axonal growth, and matrix metalloproteinases (MMPs) are the most important class of proteases that break down the extracellular matrix. This experiment was to study the effect of nourishing liver-kidney Chinese herbal medicine Fujian tablets on the expression of MMP-2 and MMP-9 in the brain of rats with focal cerebral ischemia, and to explore the mechanism of Fujian tablets in the treatment of ischemic stroke. METHODS: Forty-nine male Wistar rats were randomly divided into sham operation group, model group (divided into 1w, 2w and 3w groups) and drug administration group (divided into 1w, 2w and 3w groups). The model group and the drug administration group were performed on the right side. Middle cerebral artery occlusion caused focal cerebral ischemia in rats. In the sham operation group, the same craniotomy was performed, but the middle cerebral artery was not closed. The rest of the operation was the same as the model group. On the 6th day after successful modeling, the drug group was intragastrically given Fujian Tablets at a dose of 9g crude drug/kg/d, and the other two groups were given intragastric administration of the same amount of normal saline, once daily. The expression of MMP-2 and MMP-9 in the brain of MCAO rats was detected by enzyme-linked immunosorbent assay after the corresponding time points. RESULTS: The activity of MMP-2 and MMP-9 in the model group was significantly different from that in the sham group after 1 week of dosing, indicating that the model was successful; the model group had no difference after 1 week, 2 weeks, and 3 weeks of drug administration; After 2 weeks and 3 weeks of treatment, there was a difference between the same group and the previous period, indicating that the activity of MMP-2 and MMP-9 gradually increased with the prolonged administration time; the activity of MMP-2 and MMP-9 in the drug group after 1 week of treatment There was no significant difference between the model group and the same period, but the expression increased significantly after 2 weeks and 3 weeks. There was a significant difference between the model group and the same period. Conclusion: The mechanism of Fujian Tablets in treating ischemic stroke may be related to the up-regulation of MMP-2 and MMP-9 expression at the later period, thereby inhibiting the formation of glial scars, which is related to the elimination of negative factors of nerve function remodeling.