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黄芪当归合剂对间质纤维化肾脏中细胞外基质降解系统的调控作用

Keywords: 黄芪当归合剂,肾间质纤维化,细胞外基质,纤溶酶原激活物抑制物-1,组织型纤溶酶原激活物,基质金属蛋白酶,组织型基质金属蛋白酶抑制剂-1

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Abstract:

目的:深入研究黄芪当归合剂抑制肾脏纤维化的作用机制。方法:Wistar雄性大鼠随机分为假手术组、单侧输尿管梗阻模型组和黄芪当归合剂治疗组(14g·kg-1·d-1)。在治疗后的第3,7,10天观察各组纤维化程度,测定纤溶酶原激活物抑制物-1(PAI-1)、组织型纤溶酶原激活物(t-PA)及活性PAI-1,t-PA的表达,检测基质金属蛋白酶(MMP-9,MMP-2)及组织型基质金属蛋白酶抑制剂-1(TIMP-1)活性。结果:黄芪当归合剂明显减轻输尿管梗阻导致的肾间质纤维化。在各时间点,模型组总PAI-1及活性PAI-1的表达较假手术组明显增高,而经黄芪当归合剂治疗后PAI-1表达及活性较模型组显著降低;模型组中t-PA仅在第3天时增高,同时黄芪当归合剂治疗组较模型组明显降低。整个观察期中模型组和黄芪当归合剂治疗组的MMP-2,9活性均较假手术组明显增高,但2组间无统计学差异;模型组的TIMP-1活性在第7天和第10天时显著增高,而黄芪当归合剂治疗组较模型组显著降低。结论:黄芪当归合剂可以改善肾组织PAs/PAIs及MMPs/TIMPs系统的失衡而减少细胞外基质的积聚,可能是其抑制肾间质纤维化的机制之一。

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