痛经宁对子宫内膜异位症大鼠在位及异位内膜中ICAM-1、MMP-9及VEGF表达的影响

目的:观察中药痛经宁对子宫内膜异位症(EMs)大鼠在位与异位内膜中细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)及血管内皮生长因子(VEGF)表达的影响。方法:自体移植法建立EMs大鼠模型,随机数字表法随机分为模型组、西药组及痛经宁低、中、高剂量组;另设正常对照组。分别给予灌胃蒸馏水、孕三烯酮及痛经宁高、中、低浓度的药液,共28 d。观察各组大鼠异位内膜的生长情况,游标卡尺测量其体积;免疫组化S-P法、免疫印迹(Western blot)法测定各组大鼠在位与异位内膜中ICAM-1、MMP-9及VEGF蛋白表达,RT-q PCR法测定ICAM-1、MMP-9及VEGF mRNA表达。结果:模型组大鼠异位内膜处出现广泛黏连及小血管生成,各用药组的黏连及小血管生成情况有不同程度的改善,以痛经宁高剂量组效果最佳;各用药组大鼠异位内膜体积较模型组有不同程度的减少,其中痛经宁高剂量组较其他药物组减少最多(P0.05)。在位及异位内膜中,模型组大鼠ICAM-1、MMP-9、VEGF蛋白及mRNA均较正常组呈高表达(P0.05),且异位内膜强于在位内膜;与模型组比较,各用药组上述指标表达均有不同程度的下降,且痛经宁高剂量组显著低于其他药物组(P0.05)。结论:痛经宁可显著缩小异位内膜的体积,改善黏连、血管生成等情况;可下调在位及异位内膜中ICAM-1、MMP-9、VEGF蛋白及mRNA表达。

Effects of Tongjingning Granule on expressions of ICAM-1,MMP-9 and VEGF in eutopic and ectopic endometrium of rats with endometriosis

  Objective:To observe the effects of Tongjingning Granule on the expressions of intercellular cell adhesion molecule-1(ICAM-1),matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in eutopic and ectopic endometrium of endometriosis(EMs)rats.   Methods:The rat model of EMs was established by autologous transplantation. According to the random number table,the model rats were divided into the model group,western medicine group and Tongjingning groups with low-, middle- and high-dose. Additionally, the normal rats were taken as the control group. The rats in each group were treated with distilled water,gestrinone, Tongjingning Decoction with low-, middle- and high-concentration,respectively. After intragastric administration for 28 days, the growth of ectopic endometrium in rats of each group was observed, and the volume of the ectopic endometrium was measured by vernier caliper. The protein expressions of ICAM-1, MMP-9 and VEGF in eutopic and ectopic endometrium were detected by immunohistochemistry(S-P) and Western blot. The mRNA expressions of ICAM-1, MMP-9 and VEGF were detected by RT-qPCR.   Results:The extensive adhesion and microangiogenesis were observed in the ectopic endometrium of rats in the model group and were alleviated in all drug treatment groups to different extent, especially in the Tongjingning group with high-dose. Compared with the model group, the ectopic endometrium volume of rats in all drug treatment groups were decreased to different extent, especially in Tongjingning group with high-dose (P<0.05). In the model group, the protein and mRNA of ICAM-1, MMP-9 and VEGF were highly expressed in both eutopic and ectopic endometrium (P<0.05), and the expressions in the ectopic endometrium were higher than those in the eutopic endometrium. Compared with the model group, these protein and mRNA expressions were decreased in all drug treatment groups to different extent, and the expressions in the Tongjingning group with high-dose were significantly lower than those in the other drug treatment groups (P<0.05).   Conclusion:Tongjingning Granule can significantly decrease the ectopic endometrium volume,improve the adhesion and microangiogenesis,and down-regulate the protein and mRNA expressions of ICAM-1, MMP-9 and VEGF in eutopic and ectopic endometrium.