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目的观察瑞舒伐他汀对局灶性脑缺血再灌注大鼠脑组织中基质金属蛋白酶9(MMP-9)和组织金属蛋白酶抑制物1(TIMP-1)表达的影响。方法将24只雄性SD大鼠随机分为假手术组、模型组和实验组,每组8只。实验组在模型制备前用瑞舒伐他汀5 mg·kg~(-1)·d~(-1)连续灌胃10 d,每天1次;假手术组和模型组予以正常喂养。模型组和实验组参考改良Zea-Longa线栓法制备大鼠大脑中动脉栓塞模型,脑缺血2 h后拔出线栓形成再灌注;假手术组接受相似手术处理,但是不插入线栓。再灌注48 h后,用半定量聚合酶链式反应法、免疫组织化学法和Western印迹法检测脑组织中MMP-9和TIMP-1的表达。结果模型组与实验组脑组织中MMP-9 mRNA表达分别为(0.45±0.04),(0.31±0.04);TIMP-1 mRNA表达分别为(0.39±0.05),(0.52±0.06),差异均有统计学意义(P<0.05)。结论瑞舒伐他汀可通过抑制MMP-9的表达,提高TIMP-1的表达,发挥神经保护作用。
Objective To observe the effect of rosuvastatin on the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in brain tissue of focal cerebral ischemia-reperfusion rats. Methods Twenty-four male SD rats were randomly divided into sham operation group, model group and experimental group, with 8 rats in each group. The experimental group was treated with rosuvastatin 5 mg · kg -1 · d -1 for 10 days once a day before model preparation. The rats in sham operation group and model group were fed with normal diet. The middle cerebral artery occlusion model was established in model group and experimental group with reference to the modified Zea-Longa thread method. After 2 h of cerebral ischemia, the thrombus was removed and reperfusion was performed. The sham-operated group received similar surgical treatment, but no thread was inserted. After 48 h of reperfusion, the expression of MMP-9 and TIMP-1 in brain tissue were detected by semi-quantitative polymerase chain reaction, immunohistochemistry and Western blot. Results The expressions of MMP-9 mRNA in the model group and the experimental group were (0.45 ± 0.04) and (0.31 ± 0.04), respectively, and those in the experimental group were (0.39 ± 0.05) and (0.52 ± 0.06) Statistical significance (P <0.05). Conclusion Rosuvastatin exerts neuroprotective effect by inhibiting the expression of MMP-9 and increasing the expression of TIMP-1.