红藤颗粒剂对子宫内膜异位症大鼠异位内膜黏附分子相关基因表达及血管内皮生长因子mRNA表达的影响

Effect of Traditional Chinese Medicine "Caulis Sargentodoxae Drug Granuleson" on Gene Expression in Adhesive Molecule and VEGFmRNA of Ectopic Endometrium in Endometriosis Model Rats

目的:探讨中药红藤颗粒剂对正常大鼠与子宫内膜异位症(EMs)大鼠异位内膜黏附分子与细胞外基质蛋白差异表达基因的干预作用和对内膜血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA表达的影响。方法:将采用手术自体移植法成功建立的EMs模型大鼠随机分为6组:模型对照组(A组)、去势组(B组)、米非司酮组(5 mg/kg,C组)、红藤颗粒剂低剂量组(20 g生药/kg,D组)、中剂量组(40 g生药/kg,E组)和高剂量组(80 g生药/kg,F组)。连续灌胃给药21 d后,采用基因芯片法检测异位内膜黏附分子与细胞外基质蛋白基因的表达,实时定量PCR法(Real-time PCR)法检测红藤颗粒剂对异位内膜VEGFmRNA表达的影响。结果:①基因芯片检测结果显示模型大鼠与正常大鼠之间有27个基因差异表达,其中7个基因下调,20个基因上调,主要分为3类:黏附分子、细胞外基质蛋白、蛋白酶以及蛋白酶抑制剂。F组显示可改善EMs大鼠的差异基因表达,降低细胞间黏附分子的表达,降低蛋白酶的表达,使其趋于正常化。②B、C、E、F组均显著降低VEGFmRNA在大鼠异位子宫内膜细胞中的表达(P<0.01)。结论:中药红藤颗粒剂可能通过影响细胞外基质蛋白以及黏附分子基因的表达,抑制异位内膜VEGF的表达,从而抑制异位内膜黏附、侵袭、血管生成,抑制异位内膜的生长,使异位内膜萎缩。

Objective：To explore the effect of Traditional Chinese Medicine ＂Caulis Sargentodoxae Drug Granules＂（CSD） on the differential expression gene of extracellular matrix,adhesive molecule and VEGFmRNA in rat ectopic endometrium by CSD.Methods：The model of endometriosis was established by Autotransplantion,the animals were randomly divided into 6 groups：model control group（group A）,ovariectomized group（group B）,mifepristone group（5 mg/kg,group C）,CSD low dose group（20 g/kg,group D）,medium dose group（40 g/kg,group E） and high dose group（80 g/kg,group F）.After consecutive treatment for 21 d,the extracellular matrix（ECM） and adhesive molecule expression were detected by gene array,and the expression of vascular endothelial growth factor（VEGF） mRNA in ectopic endometrium for each group was detected by Realtime PCR.Results：1）Gene array results showed there were 27 differentially expressed genes,7 down-regulated genes and 20 up-regulated genes between model rats and normal rats,which could be divided into three main categories：adhesion molecules,extracellular matrix proteins,protease and protease inhibitors.CSD high dose group（Group F） could improve the differential gene expression in endometriosis rats,and could reduce the expression of cell adhesion molecules.It could also reduce the expression of proteases,and tend to normalize those expressions. 2）The expression level of VEGF mRNA in ectopic endometrium in group B,C,E or F was significantly lower than that in group A（P0.01）.Conclusion：CSD may hold-back the genetic expression of ECM and adhesive molecule, and inhibit the expression of VEGF in ectopic endometrium.CSD then make interference in the ectopic endometrium＇s adhesion,invasion and angiogenesis.Finally it can inhibit the ectopic endometrium growth and induce the atrophy of explants in the endometriosis model rats.