Objective To determine the effects of hypobaric hypoxia pretreatment on surgically induced endometriosis in rats. Methods Six rats were randomized into 2 groups and exposed to hypoxia (8%O2) and normoxia (21%O2) for 8 h. The uterine endometrium was intraperitoneally implanted into estrogen-treated ovariectomized Lewis rat, and the growth and quality of the implants were measured. The changes in apoptosis, protein and gene expressions in the serum, abdominis effusion fluids and implants were tested by ELISA, immunohistochemical staining, TUNNEL assay, Western blotting and RT-PCR. Results The volume of the implants in the hypoxic pretreatment group was significantly increased compared with the normoxia group. High expressions of Ki67, CD31, VEGF, and HIF-1αand lowered cell apoptosis were found in the hypoxia-pretreated implants compared with the normoxic group. VEGF level in the serum and peritoneal fluid were increased in hypoxia-pretreated group, but TNFαlevel was comparable between the 2 groups. Conclusion Hypoxia play an important role in the occurrence and progression of endometriosis by increasing cell proliferation and angiogenesis and decreasing cell apoptosis in the implants in the rat model.%目的：了解低氧预处理（hypoxic preconditioning, HPC）对子宫内膜异位症（EMs）大鼠模型异位病灶形成的影响，藉此进一步阐明EMs发生发展的分子机制，从而为其防治供新思路。方法 Lewis雌性大鼠随机分为两组，分别给予HPC（8%O2）和常压常氧（21%O2）处理8 h，随即取其子宫组织移植至正常大鼠腹壁。术后14 d记录移植灶体积，并采用ELISA、免疫组化、Western blot、RT-PCR和Tunnel法，对血清和腹腔液以及移植前子宫组织和移植病灶进行检测。结果 HPC可显著上调大鼠子宫血管内皮生长因子（VEGF）mRNA（P<0.01），并增加其低氧诱导因子（HIF）-α（P<0.01）表达；与未经HPC的比较，由经HPC的子宫组织所形成的移植病灶体积显著增大（P<0.01），组织细胞凋亡率减少（P<0.01），VEGF mRNA上调（P<0.01），HIF-α（P<0.01）、VEGF （P<0.05）、CD31（P<0.01）、Ki67（P<0.01）及Bcl-2（P<0.05）表达均明显增加；且移植了经HPC子宫组织的大鼠血清及腹腔积液VEGF含量也明显增加（P<0.01）。结论 HPC可通过激活HIF-1α/VEGF体系，促进移植病灶内血管生成；并通过上调Bcl-2抑凋亡因子表达，抑制移植病灶组织细胞凋亡，并促进其增殖，从而促进移植病灶的生长。基于此，我们推测对于EMs高风险对象或复发患者而言，避免其在位内膜组织反复接受低氧刺激，以及内膜组织脱落前即人为干预抑制HIFs/VEGF体系活化，有望成为控制EMs发生发展的措施之一。
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