消瘤方对子宫内膜异位症大鼠盆腔粘连的影响

Effect and the mechanism of Xiaoliu decoction on pelvic adhesion in rats with endometriosis

目的:探讨消瘤方对子宫内膜异位症大鼠模型盆腔粘连的影响及机制。方法:采用自体移植构建盆腔子宫内膜异位症大鼠模型,分别使用不同剂量的消瘤方提取物[1.89、3.78 g/(kg·d)],米非司酮混悬液及0.9%氯化钠溶液连续灌胃4周后剖腹探查。采用美国生殖医学会粘连分级(AFS)、Haber评分法对盆腔粘连情况进行评估,酶联吸附(ELISA)法检测大鼠血清中白介素-6、白介素-15、白介素-18、粘连组织组织型纤溶酶原激活剂(tPA)活性,免疫组化法检测血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)、细胞间黏附分子1(ICAM1)表达水平、微血管密度计数(MVD)。结果:与空白对照组相比,米非司酮和消瘤方处理大鼠后的盆腔粘连评分明显降低,血清中IL-6、IL-15、VEGT、TNF-α、ICAM1等表达水平均明显降低,血清中IL-18、粘连组织tPA活性均升高(P<0.05),异位内膜组织VEGF、TNF-α、ICAM1蛋白表达水平、微血管密度计数均显著降低(P<0.05);与低剂量消瘤方组[1.89 g/(kg·d)]相比,高剂量消瘤方组[3.78 g/(kg·d)]和米非司酮组,盆腔粘连评分高,异位病灶生长好,血清各细胞因子水平表达均降低,IL-18、异位内膜组织VEGF、TNF-α、ICAM1蛋白表达、tPA活性高(P<0.05);高剂量消瘤方组和米非司酮组在病灶生长情况、盆腔粘连评分、血清各细胞因子水平及异位组织蛋白表达无统计学差异(P>0.05)。结论:消瘤方能明显减轻盆腔炎症环境,抑制内异症病灶生长、改善盆腔粘连。

Objective:To explore the effect and mechanism of Chinese medicine Xiaoliu decoction on pelvic adhesion in rats with endometriosis.Methods:Pelvic endometriosis rats with auto-transplantation successfully were deal with different doses of Xiaoliu decoction[1.89,3.78 g/(kg·d)],mifepristone suspension and 0.9%NaCl solution,continuous intragastric for 4 weeks and then laparotomy was performed.The pelvic adhesion was evaluated by the American Society for Reproductive Medicine Classification of Endometriosis(AFS)and Haber adhesion score.Serum Interleukin-6、serum Interleukin-15、serum Interleukin-18(IL-6,IL-15,IL-18)、vascular endothelial growth factor(VEGF),tumor necrosis factor-a(TNF-α),intercellular adhesion molecule-1(ICAM1),the actives of tissue-type plasminogen activator(tPA)of adhesion tissues were detected by enzyme-linked adsorption(ELISA),the protein expression of VEGF,TNF-α,ICAM1 and microvessel density(MVD)were measured by immunohistochemistry.Results:Compared with blank control group,the pelvic score of rats treated with mifepristone and Xiaoliu decoction were significantly decreased,and expression of IL-6,IL-15,VEGF,TNF-α,ICAM1 of serum were significantly decreased,the levels of IL-18 of serum、the activity of tPA in adhesion were higher(P<0.05),the levels of protein expression of VEGF,TNF-α,ICAM1,and the microvessel density count were significantly decreased(P<0.05).Compared with high-dose Xiaoliu decoction group[3.78 g/(kg·d)]and mifepristone group,the low-dose Xiaoliu decoction group[1.89 g/(kg·d)]had better growth of ectopic lesions,higher pelvic adhesion score,higher levels of serum cytokines,lower level of serum IL-18 and protein expressions of VEGF,TNF-α,ICAM1 and tPA activity in the ectopic intima tissues(P<0.05)。While there was no obviously difference between high-dosage Xiaoliu decoction group and mifepristone group in ectopic lesion growth,pelvic adhesion score、levels of serum cytokines and ectopic tissues protein expression(P>0.05)。Conclusion:Xiaoliu decoction can significantly relieve the inflammatory environment of pelvic,inhibit the growth of internal abnormal lesions and improve pelvic adhesion.