中文摘要：

目的：在大鼠模型基础上,探索重组色素上皮源性因子（rPEDF）对子宫内膜异位病灶（EM）的治疗价值和作用机制。方法：建立大鼠 EMs 模型,随机分为对照组（仅给予 PBS,n =5）、治疗Ⅰ组（建模后立即开始给予 rPEDF）及治疗Ⅱ组（建模后1周开始给予 rPEDF）。根据给药剂量,治疗Ⅰ、Ⅱ组均设立10μg / kg、25μg / kg、50μg / kg 3个亚组（各亚组 n =5）,隔日一次尾静脉注射。造模后3周测量异位病灶体积,RT-PCR 及Western blot 法检测血管内皮生长因子（ VEGF）及 FasL mRNA 及蛋白表达水平。评估rPEDF 对 EM 大鼠及非 EM 大鼠动情周期、排卵、着床等生殖生理参数的影响及内膜异位病灶的治疗价值。结果：治疗Ⅰ组中25μg / kg rPEDF 即可显著减小异位病灶体积,并随剂量增加呈量效关系,治疗Ⅱ组给药剂量达50μg / kg 时才具有显著差异；且同等治疗剂量下,治疗Ⅰ组的病灶体积显著小于治疗Ⅱ组（P 均〈0.01）。给药剂量为25μg / kg 时,各治疗组的 VEGF 表达水平较对照组显著降低,并呈量效关系；且相同治疗剂量下,治疗Ⅰ组的 VEGF 表达水平显著低于治疗Ⅱ组（P 均〈0.01）；给药剂量为50μg / kg 时,各治疗组FasL mRNA 及蛋白的表达水平显著高于对照组（P 均〈0.01）,治疗Ⅰ组、Ⅱ组间无显著差异（P〉0.05）。50μg / kg rPEDF 对大鼠动情周期、排卵无影响,并可显著改善 EM 大鼠着床率（P〈0.05）。结论：补充外源性 rPEDF 可有效抑制 EM 模型大鼠内膜异位病灶的发生发展,病变早期给药效果更好,最佳给药剂量为50μg / kg,且该剂量不会对大鼠生殖参数造成不良影响。

英文摘要：

Objective：To explore the values of recombinant pigment epithelium-derived factor （ rPEDF） in the therapy of endometriosis（ EM） and the underlying mechanisms based on rat models. Methods：Endometriosis was induced by transplanting the endometrial pieces onto the peritonea of female SD rats. The EM rat models were randomly injected intravenously every other day with either PBS （control group,n=5） or recombined PEDF （rPEDF） in a series of concentrations of 10μg/kg,25μg/kg,50μg/kg right after grafting （ therapy group I, n=5 in each concentration） . Or rPEDF injections with the same concentration series as the above were started 1 week after operation （ therapy group II, n=5 in each concentration ） . 3 weeks after grafting,the rats were sacrificed to measure the sizes of lesions,to detect the mRNA and protein levels of vascular epithelium growth factor （ VEGF） and FasL genes. Moreover,the effects of rPEDF on the estrous cycle,ovulation and embryo implantation of the rats with or without EM were also evaluated. Result：In therapy group I,supplement of rPEDF （25μg/kg or more） ever-y other day could significantly reduce the sizes of EM lesions in a dose-dependent manner （ P〈0. 01）. While in therapy group II,rPEDF exhibited a significant inhibitory function only in 50μg/kg subgroup （P〈0. 01）. In both therapy I and II groups,rPEDF of no less than 25μg/kg dose-dependently suppressed the level of VEGF mRNA or protein（P〈0. 01）. Moreover,the le-sion sizes or VEGF expression was statistically decreased in therapy group I compared with ther-apy group II when the same doses of rPEDF were given （ P〈0 . 01 ） . The expressions of FasL mRNA and protein were significantly induced only in the 50 μg/kg subgroups （P〈0. 01）,with no statistical difference between therapy group I and II （P〉0. 05）. Meanwhile,it was also ob-served that rPEDF of 50μg/kg had no adverse effects on the estrous cycle or ovaluation of rats with or without EM. The impaired embryo implant