蒲灵化瘀止痛方治疗小鼠子宫腺肌病的药效学观察

Pharmocodynamic Observation of Puling Huayu Zhitong Prescription on Adenomysis Mice

摘要:

目的: 以雌激素效应相关因子、血管生成相关因子及其相互作用为靶点,探讨蒲灵化瘀止痛方治疗子宫腺肌病(AM)的作用机制及其量效关系. 方法: 选择8周龄ICR雌鼠,随机分为5组,正常组、模型组、蒲灵化瘀止痛方(蒲方)高、中、低剂量组(60,30,15 g·kg^-1),除正常组外,均采用垂体宫腔内移植手术造模,术后3月,形成AM模型.分组给药3月,运用免疫组化技术观察不同用药剂量下雌激素效应相关因子及血管生成相关因子的变化. 结果: 与正常组比较,模型组在位及异位内膜细胞色素P450(P450),环氧化酶-2(COX-2),雌激素受体a(ERa)均显著上调(P<0.05).模型组异位内膜与在位内膜比较,P450显著上调(P<0.05).模型组在位内膜与正常组内膜比较,血小板内皮细胞黏附因子CD31(CD31)显著下降,血管内皮生长因子(VEGF)及基质金属蛋白酶2(MMP-2)显著上调(P<0.05).无论在位或异位内膜,与模型组比较,蒲方各给药组P450,COX-2,ERa值均显著下降(P<0.05),除在位内膜COX-2外,各剂量组之间比较无显著差异.与模型组比较,蒲方给药组在位内膜CD31显著升高(P<0.01),高剂量组显著优于其余两组(P<0.01);蒲方给药组异位内膜VEGF及MMP-2显著下调,高剂量组显著优于低剂量组(P<0.05). 结论: 改善局部缺血缺氧的作用、对血管生成相关因子的调控程度与蒲灵化瘀止痛方剂量相关,雌激素效应因子与该方剂量无显著相关性.

Abstract:

Objective: To observe the expression of estrogen effect correlator(EFC) and angiogenesis correlator(AC),and investigate the mechanism of different doses of Puling Huayu Zhitong prescription (PLP) at the different position of the endomembrane in adenomysis(AM) mice. Method: AM mouse model was established by pituitary intrauterine transplant operation.The mice were divided into five groups 3 months after modeling:the normal group, the model group and the high, medium,low dose groups of PLP. The express of EFC and AC was detected by method of immunohistochemisty dyeing. Result: Whether in ectopia or eutopia endometrium, the express of cytochrome P450 proteins (P450), cyclo-oxygen-ase 2(COX-2), estrogen receptor a (ERa) increased dramatically after treatment compared to model group, ther was no significant difference among three therapeutics groups except the express of COX-2 in eutopia endometrium. The expression of platelet endothelial cell adhesion molecule CD31(CD31)increased notably in eutopia endometrium after treatment compared to the model group, the increased extent of CD31 in high dose group was higher than that in medium and low dose groups. In ectopia endometrium, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases-2(MMP-2) decreased significantly in group high dose group compared to group low dose group after treatment. Conclusion: The dose of PLF is correspond with the action of improvement of ischemia, anoxemia, and with the regulation of the AC,which has no associativity with EFC.