Reproductive and Vascular Biology Group, Institute of Cellular Medicine, Newcastle University, 3rd Floor, William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.
Angiogenesis. 2011 Dec;14(4):523-32. doi: 10.1007/s10456-011-9237-x. Epub 2011 Oct 9.
Uterine natural killer (uNK) cells and endometrial blood vessel maturation are increased in the luteal phase of the menstrual cycle in a subset of women with recurrent miscarriage (RM). uNK cell numbers are reduced after treatment with prednisolone (20 mg/day for 3 weeks).
Prednisolone treatment reduces endometrial vascular maturation and angiogenic growth factor expression in women with RM with increased uNK cells.
Endometrial biopsies (n = 18 paired samples) from women with RM at LH + 7 before and during prednisolone treatment (20 mg/day for 3 weeks) were snap frozen. Total RNA and cDNA was prepared and used in a human angiogenesis RT-PCR superarray (84 genes, n = 6 pairs) with results validated using RT-PCR (n = 15 pairs). Immunohistochemistry (n = 15 pairs) was performed for Factor VIII, α-smooth muscle actin (α-SMA) and myosin heavy chain (MyHC) and the total number of vessels and the percentage of vessels completely surrounded by vascular smooth muscle cells (VSMCs) were determined.
During prednisolone treatment there was no change in the total number of endometrial blood vessels but the percentage of vessels completely surrounded by VSMCs was decreased (α-SMA P < 0.0001; MyHC P < 0.0001). Endometrial EGF and STAB 1 expression was decreased during prednisolone treatment in samples from woman who went on to have a live birth.
The effect of prednisolone therapy for some women with RM may be due to altered endometrial angiogenic growth factor expression and reduced blood vessel maturation.
在一些反复性流产(RM)患者的黄体期,子宫自然杀伤(uNK)细胞和子宫内膜血管成熟度增加。经泼尼松龙(每天 20 毫克,治疗 3 周)治疗后,uNK 细胞数量减少。
泼尼松龙治疗可降低 RM 患者中 uNK 细胞增多的子宫内膜血管成熟度和血管生成生长因子表达。
在 LH + 7 时,对 RM 患者的子宫内膜活检(n = 18 对样本)进行前和泼尼松龙治疗期间(每天 20 毫克,治疗 3 周)的即刻冷冻。提取总 RNA 和 cDNA,并用人类血管生成 RT-PCR 超级阵列(84 个基因,n = 6 对)进行分析,结果使用 RT-PCR 进行验证(n = 15 对)。对因子 VIII、α-平滑肌肌动蛋白(α-SMA)和肌球蛋白重链(MyHC)进行免疫组织化学(n = 15 对),并确定血管总数和完全被血管平滑肌细胞(VSMC)包围的血管百分比。
在泼尼松龙治疗期间,子宫内膜血管总数没有变化,但完全被 VSMC 包围的血管百分比减少(α-SMA P < 0.0001;MyHC P < 0.0001)。在泼尼松龙治疗期间,子宫内膜 EGF 和 STAB 1 的表达下降,这些患者后来继续有活产。
对于一些 RM 患者,泼尼松龙治疗的效果可能是由于子宫内膜血管生成生长因子表达改变和血管成熟度降低所致。