桂枝茯苓丸抑制子宫内膜异位症模型大鼠异位病灶侵袭转移的机制

Mechanism of Guizhi Fuling Pill on Inhibiting Invasion and Metastasis of Endometriosis in Rats

目的:分析桂枝茯苓丸抑制大鼠子宫内膜异位症侵袭转移的作用机制。方法:采用自体移植法建立大鼠子宫内膜异位症模型,分为模型对照组、桂枝茯苓丸高剂量组、桂枝茯苓丸低剂量组、孕三烯酮组,另外设假手术组。给药28 d后处死大鼠,测量并计算异位病灶大小,实时定量PCR法检测大鼠异位内膜组织中侵袭和转移相关基因基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、金属蛋白酶组织抑制因子-1(tissue inhibitor of matrix metalloprotease-1,TIMP-1)、尿激酶型纤溶酶原激活物(urokinase plasminogen activator,uPA)和纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)的表达水平。酶联免疫吸附法检测腹腔液肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(interleukin-1β,IL-1β)的水平。结果:桂枝茯苓丸高剂量组、低剂量组异位内膜中MMP-9和PAI-1的表达水平低于模型对照组,差异有统计学意义(P<0.05);TIMP-1表达水平高于模型对照组,差异有统计学意义(P<0.05);腹腔液中TNF-α和IL-1β的水平低于模型组,差异有统计学意义(P<0.05)。结论:桂枝茯苓丸可能通过下调异位内膜中MMP-9和PAI-1的表达,上调TIMP-1的表达,降低腹腔液中TNF-α和IL-1β的水平抑制子宫内膜异位症的侵袭和转移。

Objective:To analyze the mechanism of Guizhi Fuling pill in inhibiting the invasion and metastasis of endometriosis in rats.Methods:The rats were divided into model control group,Guizhi Fuling pill high-dose group,Guizhi Fuling pill low-dose group,gestrinone group,and sham operation group.After 28 days,the rats were killed and the size of ectopic lesions was measured and calculated.Matrix metalloproteinase-9(MMP-9),tissue inhibitor of matrix metalloproteinase-1(TIMP-1),urokinase plasminogen activator(uPA)and the expression level of plasminogen activator inhibitor-1(PAI-1)in ectopic endometrium of rats were detected by real-time quantitative PCR.The levels of tumor necrosis factor-α(TNF-α)andinterleukin-1β(IL-1β)in peritoneal fluid were measured by enzyme-linked immunosorbent assay.Results:The expression levels of MMP-9 and PAI-1 in the ectopic endometrium of Guizhi Fuling Pills in the high-dose and low-dose groups were lower than those in the model control group,and the difference was statistically significant(P<0.05);the expression level of TIMP-1 was higher than the model in the control group,the difference was statistically significant(P<0.05);the levels of TNF-αand IL-1βin the peritoneal fluid were lower than the model group,and the difference was statistically significant(P<0.05).Conclusion:Guizhi Fuling pill may inhibit the invasion and metastasis of endometriosis by down regulating the expression of MMP-9 and PAI-1,up regulating the expression of TIMP-1,and decreasing the levels of TNF-αand IL-1βin peritoneal fluid.