来氟米特对子宫内膜异位症大鼠模型作用机制的研究

目的观察来氟米特用于子宫内膜异位症(endometriosis,EMT)大鼠模型的整个影响过程,检测模型异位灶中p-STAT和SOCS mRNA表达情况,探讨来氟米特对子宫内膜异位症的作用机制。方法采用自体移植法建立大鼠子宫内膜异位症模型,移植后第4周开腹建模成功的大鼠并随机分为空白对照组(每天0.15%羧甲基纤维素水1 ml/kg)、来氟米特高剂量组(每天35 mg/kg)、低剂量组(每天10 mg/kg)及阳性对照组(达那唑组每天25 mg/kg),连用3周,测量用药前后病灶体积,并采用Western blot和RT-PCR法分别检测异位子宫内膜灶中p-STAT蛋白和SOCS mRNA表达情况。结果来氟特高剂量组和达那唑组大鼠异位灶体积较空白对照组明显缩小(P<0.05),SD大鼠异位内膜p-STAT蛋白表达均低于对照组(P<0.05),而且SOCS-1 mRNA表达也均低于对照组(P<0.05)。结论来氟米特对对子宫内膜异位灶生长行为有抑制作用,而其发挥这种作用的机制可能是通过抑制子宫内膜移位灶JAK/STAT信号转导途径来实现的。

The effects of leflunomide on endometriosis and its mechanism in rat model

This study is aimed to explore the action mechanism of immunomodulator leflunomide in the development of an experimental endometriosis model.Firstly,endometriosis(EMT) model was set up by surgically transplanting autologous fragments of endometrial tissue onto the inner surface of the abdominal wall and arterial cascades of the small intestines.With the application of Western blot method and RT-PCR method,we detected the expressions level of phosphorylation of STAT(p-STAT) protein and cell signaling inhibitory factor(SOCS)-1 mRNA in ectopic endometrium of rats with EM and controls.At the same time,we inspected the change of ectopic endometrium volume in rats,and found that the ectopic endometrium volume of treatment group and danazol rats was significantly decreased than that in control group(P < 0.05).In leflunomide high-dosage group,the expression of p-STAT was lowered,the histopathological changes were improved,and the expression of SOCS-1 mRNA was increased significantly as compared with control group(P < 0.05).From these results,we presumed that leflunomide can inhibit the ectopic endometrium volume of rats with endometriosis.Furthermore,leflunomide can inhibit the expression of p-STAT and prevent the excess activation of JAK/STAT signal transduction pathway,which may be one of the mechanisms for the therapeutic effects in the experimental endometriosis model.