靶向NF-κB的小干扰RNA抑制人子宫内膜异位症体外血管生成模型的实验研究

Small interference RNA targeting nuclear factor-κB inhibits endometriotic angiogenesis in chick embryo chorioallantocic membrane

目的探讨NF-κBp65 siRNA对子宫内膜异位症(EMs)血管生成的抑制作用,为抗血管途径治疗EMs提供依据。方法将EMs患者在位子宫内膜组织接种于8d胚龄的鸡胚绒毛尿囊膜(CAM)上,建立EMsCAM模型,分设空白组、单纯接种组、阳性siRNA干预组和阴性siRNA干预组。通过Image-proplus软件测量新生血管面积与鸡胚尿囊膜面积比(VA/CAM)及组织病理学观察等方法评价沉默NF-κB基因对CAM血管生成及异位内膜病灶生长行为的影响。结果各组VA/CAM分别是(22.18%±1.51)%、(30.28±3.91)%、(10.36±2.18)%及(28.60±4.22)%。组间比较:阳性干预组VA/CAM均低于其余3组,差异有显著性(P<0.05);接种组及阴性干预组VA/CAM均高于空白组,差异有显著性(P<0.05);接种组与阴性干预组间比较差异则无显著性(P>0.05)。阳性干预组病灶在光镜下可见腺体完整性破坏。结论NF-κB参与调控子宫内膜异位症的发生发展,沉默NF-κB基因可以显著抑制异位病灶的血管形成,并干扰子宫内膜的异位生长,抗血管途径可能成为治疗EMs的有效策略之一。

Objective To investigate the effect of small interference RNA （siRNA） targeting nuclear factor-KB （NF-KB） on endometriosis. Methods The eutopic endometrium of women with endometriosis were transplanted into the nonvascular region of 8-day-old chicken embryo chorioallantocic membrane （CAM）, and the effects of NF-KB p65 siRNA on the vascularization and endometriotic lesion formation were tested with proper controls. Results Transplantation of the endometrium onto the CAM resulted in a strong angiogenic response in the chicken tissue. The angiogenesis was significantly reduced and endometriotic lesion formation significantly suppressed with siRNA targeting NF-KB in comparison with the control group. Conclusions The NF-KB pathway is involved in the development of endometriotic lesions in vitro, and NF-KB gene silencing reduces endometriotic angiogenesis and promotes cell apoptosis in the endometriotic lesions,suggesting that NF-KB might be a good target for endometriosis treatment.