摘要
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(14 g.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。
Objective: The imbalance between extracellular matrix(ECM) synthesis and degradation induces the excessive ECM deposition and thus renal fibrosis.The decoction(A&A) which is a combination of two Chinese herbs,Astragalus membranaceus var.mongholicus and Angelica sinensis,has been shown to alleviate ECM production in animal models of chronic kidney diseases.In this paper,the effect of A&A on ECM degradation was investigated with interstitial fibrosis in rats.Method: Male Wistar rats were randomly divided into sham,unilateral ureteral obstruction(UUO) and UAA(UUO plus A&A administration) groups.After administration of A&A(14 g·kg-1·d-1) by gavage for 3,7 and 10 days,morphological changes were evaluated by HE,PAS and Sirius red staining technique.The expression of plasminogen activator inhibitor-1(PAI-1) and tissue-type plasminogen activator(t-PA),the activity of PAI-1 and t-PA were determined by ELISA.The activity of matrix metalloproteinases(MMP-9,MMP-2),tissue inhibitor of matrix metalloproteinase-1(TIMP-1) were evaluated by gelatin zymography or reverse gelatin zymography,respectively.Result: Morphological analysis showed severe interstitial mononuclear cells infiltration,tubular atrophy,renal fibrosis and collagen expression in kidneys of UUO group,which was reduced by A&A administration(P<0.05,UAA vs UUO group).Compared with the sham group,the expression of PAI-1 was significantly increased in UUO group by 63%,91% and 112% at day 3,7 and 10 respectively;and there were a remarkable decrease in UAA group by 44%,43% and 52% at day 3,7 and 10.The expression of active PAI-1 was strikingly increased in UUO group at day 3[(30.5±23.8) ng·g-1 vs.(0.0±0.0) ng·g-1,P<0.05)],day 7[(36.5±11.2) ng·g-1 vs.(0.0±0.0) ng·g-1,P<0.05)],and day 10[(54.5±14.2) ng·g-1 vs.(0.5±0.5) ng·g-1,P<0.05)].The active PAI-1 was decreased in UAA group at day 7[(14.9±0.5) ng·g-1 vs.(36.5±11.2) ng·g-1,P<0.05] and day 10[(15.4±4.8) ng·g-1 vs.(54.5±14.2) ng·g-1,P<0.05].The expression of t-PA was increased in UUO group only at da
出处
《中国中药杂志》
CAS
CSCD
北大核心
2012年第1期79-84,共6页
China Journal of Chinese Materia Medica
基金
国家自然科学基金重点项目(30330710)
关键词
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-
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-
Astragali Radix and Angelicae Sinensis Radix decoction
renal tubulointerstitial fibrosis
excellular matrix
plasminogen activator inhibitor-1
tissue-type plasminogen activator
matrix metalloproteinase
tissue inhibitor of metalloproteinase-1
