桂枝茯苓丸治疗大鼠子宫内膜异位症的机制研究

Mechanism Research on Treatment of Guizhi Fuling Pills for Endometriosis in Rats

目的:探讨桂枝茯苓丸对子宫内膜异位症(EMS)大鼠止疼痛的作用机制及对基质金属蛋白酶表达的影响。方法:复制大鼠模型,分为模型组,芬必得组(0.054 g·kg-1),丹那唑组(0.036 g·kg-1),桂枝茯苓丸低、高剂量组(含生药0.256,1.024 g·kg-1),连续ig给药4周,放免法测定大鼠血浆中6-酮前列腺素F1α(6-keto-PGF1α),β-内啡肽(β-EP),血栓素B2(TXB2),剥取大鼠异位内膜组织,测定体积,并检测基质金属蛋白酶-2(MMP-2),基质金属蛋白酶-9(MMP-9)在异位内膜的表达。结果:桂枝茯苓丸各组异位内膜体积明显减小(P<0.01);桂枝茯苓丸各剂量组均能升高大鼠血浆6-keto-PGF1 a,β-EP水平,降低TXB2水平(P<0.01);桂枝茯苓丸各剂量组MMP-2及MMP-9表达阳性强度均降低(P<0.05,P<0.01)。结论:桂枝茯苓丸能抑制异位内膜的生长,其作用机制可能与抑制内膜组织中MMP-2及MMP-9表达有关;桂枝茯苓丸止痛机制可能是通过平衡前列腺素水平,缓解子宫平滑肌痉挛,升高内啡肽实现的。

Objective： To study the influence of Guizhi Fuling pills （GFP） on pain and matrix metalloproteinases expression in rats with endometriosis. Method： Rat model of endometriosis （EMS） was established. The model rats were divided into the model group, ibuprofen group （0. 054 g ·kg^-1） , danazol group （0. 036 g ·kg^-1 ） , and GFP low, high dose groups （0. 256, 1. 024 g ·kg^-1 ）. The treatment in each group was lasted for 4 weeks. Plasma 6-ketone prostaglandin F1α （6-keto-PGF1α）, beta endorphins （beta EP） and thromboxane B2 （TXB2） were determined by radioimmunoassay. Tissue of uterus endometriosis was obtained, and lesions and size were evaluated. The expression of matrix metalloproteinases-2 （MMP-2） and matrix metalloproteinases-9 （MMP-9） in ectopic endometrium was determined. Result： GFP could reduce the volume of ectopic endometrium significantly （P 〈 0.01 ）. Two doses of GFP could increase plasma 6-keto-PGF1α, beta EP level, and reduce TXB2 level （P 〈0.01）. Two doses of GFP could reduce the expression of MMP-2 and MMP-9 （P 〈0.05, P 〈 0.01）. Conclusion： GFP inhibits the growth of ectopic endometrium. The mechanism may be related to inhibition of the expression of MMP-2 and MMP-9. The pain relieving of GFP may be obtained through the balance prostaglandin level, alleviation of spasms of smooth muscle, and elevation of endorphins.