染料木黄酮对大鼠异位子宫内膜组织中MMP-9、TIMP-1表达的影响

目的:探讨染料木黄酮(GEN)对患子宫内膜异位症(EMs)大鼠的基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶抑制剂-1(TIMP-1)表达水平的影响。方法:将68只Wistar大鼠分为正常组(A组,n=8)和EMs组(n=60),EMs组通过手术方法建立大鼠EMs模型,3周后测量移植物体积。EMs组大鼠随机分为4亚组:模型组(B组)和GEN低剂量组(C组,0.5mg/kg)、GEN中剂量组(D组,5mg/kg)、GEN高剂量组(E组,50mg/kg),连续皮下注射药物84d后处死大鼠,测量移植物体积、观察其组织学结构,并采用免疫组化法观察异位内膜组织中MMP-9、TIMP-1的表达。结果:与治疗前比较,E组移植物体积明显缩小(P<0.01),而C组和D组无差异;与A组比较,B组MMP-9表达率明显升高(P<0.05),TIMP-1表达率明显降低(P<0.01);与B组比较,E组MMP-9表达率明显降低,TIMP-1表达率明显升高(P<0.05),C组和D组无差异。结论:GEN可抑制大鼠EMs模型中异位内膜的生长,其抑制作用可能与MMP-9表达下降和TIMP-1表达升高,平衡MMP-9和TIMP-1的表达比例有关。

Effect of genistein on expression of MMP-9/TIMP-1 in rats with endometriosis

Objective ： To explore the effect of genistein （GEN） on levels of matrix metallo proteinase - 9 （ MMP - 9） and tis-sue inhibitor of metallo proteinase - 1 （ TIMP - 1 ） in rats with endometriosis （EMs）. Methods ： A total of 68 adult female Wistar rats were divided into the control group （group A, n = 8 ） and EMs group （n = 60） , in which surgically induced EMs model was established. The rats in EMs group were divided into model group （group B）, low dose GEN group （group C, 0. 5mg/kg） , middle dose GEN group （group D, 5mg/kg） and high dose GEN group （group E, 50mg/kg）. After daily ad- ministration of the corresponding agent for 84 days, the rats were sacrificed. The implant size of ectopic endometrium was measured and histological structure examination was conducted. The levels of MMP - 9 and TIMP - 1 were evaluated with im- munohistochemistry. Results： After treatment, the implant size were significantly smaller in group E （P 〈 0.01 ） , and there was no significant difference between group C and group D （P 〉 0.05 ）. Compared with group A, MMP -9 expression level was significantly higher （P 〈0.01 ） and TIMP- 1 expression level was significantly lower in group B. Compared with group B, MMP -9 expression level in group E was significantly lower, and the TIMP - 1 expression level was significantly higher （P all 〈 0. 05 ）. There were no significantly differences in MMP - 9 and TIMP - 1 expression levels between group C and group D. Conclusion ： High dose of GEN could inhibit the development of ectopic endometrium in rats, and the possible mechanism maybe related to down - regulation of MMP - 9 expression and up - regulation of TIMP - 1 expression as well as promotion of the balance between MMP- 9 and TIMP- 1.