安宫牛黄丸对实验性脑出血大鼠血肿周围组织中MMP-9和AQP-4蛋白表达的影响

Influences of An Gong Niu Huang Wan on expressions of MMP-9 and AQP-4 in rats with experimental intracerebral hemorrhage

目的研究安宫牛黄丸对实验性脑出血大鼠血肿周围组织中基质金属蛋白酶(MMP-9)和水通道蛋白-4(AQP-4)表达的影响。方法采用大鼠尾状核内注入胶原酶诱发脑出血模型,术后3 h灌胃给予安宫牛黄丸(0.2、0.4 g/kg)1次,术后连给3 d,每天给药1次,3 d后采用心脏灌流多聚甲醛固定后取脑,制作石蜡切片,应用免疫组织化学方法观察血肿周围脑组织中MMP-9和AQP-4蛋白的表达。结果与假手术对照组比较,胶原酶诱导脑出血模型组动物血肿周围脑组织中MMP-9(P<0.01)和AQP-4(P<0.01)蛋白的表达明显增多,而与脑出血模型组比较,安宫牛黄丸大、小剂量组大鼠血肿周围脑组织中MMP-9(P<0.01)和AQP-4(P<0.01)表达显著降低。结论安宫牛黄丸能够抑制脑出血后血肿周围脑组织中MMP-9和AQP-4蛋白的表达,这可能与其对抗脑出血损伤有关。

Objective To study the influences of An Gong Niu Huang Wan on the expressions of matrix metallopeptidase-9（MMP-9） and aquaporin-4（AQP-4） in brain tissue around hematoma in rats with experimental intracerebral hemorrhage（ICH）.Methods The model of ICH was established by the injection of collagenase in rat caudate nucleus.An Gong Niu Huang Wan（0.2 g/kg and 0.4 g/kg） was given intragastrically to rats 3 hours after the injection,once a day for three days.The paraffin sections were prepared by using cardiac perfusion of paraformaldehyde for fixation and collection of brain samples after three days.The expressions of MMP-9 and AQP-4 were observed by using immunohistochemistry method.Results Compared with the sham-operation group,the expressions of MMP-9（P〈0.01） and AQP-4（P〈0.01） increased significantly in the model group.Compared with the model group,the expressions of MMP-9（P〈0.01） and AQP-4（P〈0.01） decreased significantly in the low-dose group of An Gong Niu Huang Wan and high-dose group of An Gong Niu Huang Wan.Conclusion An Gong Niu Huang Wan can inhibit the expressions of MMP-9 and AQP-4 in brain tissue around hematoma after ICH,which may be related to that it can antagonize the lesion of intracerebral hemorrhage.