蒲灵化瘀止痛方对子宫腺肌病模型小鼠异位和在位内膜血管生成相关因子的影响

摘要

目的：探讨蒲灵化瘀止痛方对子宫腺肌病(Adenomyosis，ADM)小鼠异位及在位内膜血管内皮生长因子(VEGF)、内皮抑素(ENS)、微血管密度(MVD)表达的影响，从血管生成相关因子的角度揭示蒲灵化瘀止痛方治疗ADM的作用机理。方法：造模饲养3个月建立小鼠ADM模型。将ADM小鼠随机分为蒲灵化瘀止痛方高、中、低剂量组，丹莪妇康煎膏组，孕三烯酮组，模型组，空白组，连续给药12周后，采用HE染色法观察不同组子宫内膜腺体与间质侵入子宫肌层的程度；采用免疫组化SP法染色检测异位和在位子宫内膜的VEGF、ENS的表达，并通过CD31标记异位子宫内膜血管内皮细胞，测定其MVD。结果：蒲灵化瘀止痛方高、中剂量组能降低模型小鼠异位和在位内膜VEGF的表达(P＜0.01)，降低模型组小鼠异位内膜VEGF/ENS的比值(P＜0.01)，有下调模型小鼠在位内膜VEGF/ENS比值的趋势。结论：蒲灵化瘀止痛方减少经量的机制可能是抑制在位内膜血管生成，减少在位内膜血管数量；蒲灵化瘀止痛方缩小病灶、减轻痛经程度的机制可能是抑制异位内膜血管生成，减少异位内膜血管数量。%Objective: To reveal the mechanism of PuLing HuaYu ZhiTong prescription in treating adenomyosis (ADM) from the angles of angiogenesis-related factors by exploring the influence of PuLing HuaYu ZhiTong prescription on the expressions of vascular endothelial growth factor (VEGF), endostatin (ENS) and microvessel density (MVD) in ectopic and eutopic endometrium of mice with ADM. Methods:ADM mice models were prepared by feeding in three months. ADM mice were randomly allocated to high, moderate and low dose groups of PuLing HuaYu ZhiTong prescription, DanEFuKang extract group, gestrinone group, the model group and the blank group, after medicating for 12 consecutive weeks, the degrees of endometrial gland and stroma invading myometrium in different groups were observed by HE staining method;the expressions of VEGF and ENS in ectopic and eutopic endometrium detected by immunohistochemical SP staining method, and MVD measured by marking vascular endothelial cells of ectopic endometrium with CD31. Results:PuLing HuaYu ZhiTong prescription in high and moderate doses could lower the expressions of VEGF in ectopic and eutopic endometrium (P<0.01), it could decrease the ratio of VEGF/ENS of ectopic endometrium of the mice in the model group (P<0.01), and showed the trend of lowering the ratio of VEGF/ENS in eutopic endometrium of the mice. Conclusion:PuLing HuaYu ZhiTong prescription reducing menstrual blood volume is through inhibiting the angiogenesis of eutopic endometrium and decreasing the number of blood vessels in eutopic endometrium. The mechanism of PuLing HuaYu ZhiTong prescription narrowing the focus and alleviating the dysmenorrheal is by inhibiting the angiogenesis of ectopic endometrium and reducing the number of blood vessels in ectopic endometrium.