Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full‐thickness injury
Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full‐thickness injury
复制标题
DOI：
10.1111/wrr.12729
复制
发表时间：
2019-09
影响因子：
2.9
通讯作者：
B. Xue;Dan-Qing Liu;Minmin Song;Guangfeng Zhao;Yun Cao;G. Yan;Jianwu Dai;Yali Hu
中科院分区：
文献类型：
--
作者：
B. Xue;Dan-Qing Liu;Minmin Song;Guangfeng Zhao;Yun Cao;G. Yan;Jianwu Dai;Yali Hu
严重的子宫损伤可能导致不孕或妊娠并发症。严重损伤子宫的结构和功能缺乏有效的修复方法。白血病抑制因子（LIF）在胚泡着床过程中起着至关重要的作用，可促进多种不同组织损伤后的再生过程。在这项研究中，我们探讨了LIF对大鼠子宫角全层损伤后再生的影响。将124只雌性Sprague-Dawley大鼠分为三组，包括假手术组（n = 34个子宫角）、PBS/胶原蛋白组（n = 90个子宫角）和LIF/胶原蛋白组（n = 124个子宫角）。分别于术后1、2、4、8、12周取材。结果显示，LIF/胶原支架增加了子宫全层缺损后2周切除部位的子宫内膜细胞和新血管形成的数量（p < 0.001 vs PBS/胶原）。术后8周，LIF/胶原支架组的子宫内膜腺体数量（35.2 ± 4.1/视野）显著高于PBS/胶原支架组（15.1 ± 1.4/视野）。LIF/胶原支架中α-平滑肌肌动蛋白（α-SMA）阳性区域的百分比（88.8% ± 9.8%）也显著高于PBS/胶原组（52.9% ± 3.7%）。LIF能提高妊娠率和胎仔数。我们还发现，LIF抑制炎症细胞的浸润，下调促炎细胞因子IL-12的表达，同时上调子宫角损伤部位的抗炎细胞因子IL-10的表达。我们的研究结果表明，LIF促进损伤后子宫的再生，这至少部分是由于其免疫调节特性。此外，LIF/胶原作为子宫损伤的替代治疗方法在临床上的应用前景值得进一步探讨。
Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full‐thickness injury. One hundred and twenty four female Sprague–Dawley rats were assigned to three groups, including a sham‐operated group (n = 34 uterine horns), a PBS/collagen group (n = 90 uterine horns), and a LIF/collagen group (n = 124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8, or 12 weeks after the surgery. The results showed that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full‐thickness defect in excision sites (p < 0.001 vs PBS/collagen). Eight weeks after the surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in the PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a‐smooth muscle actin (a‐SMA)‐positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down‐regulated the pro‐inflammatory cytokine IL‐12 expression while up‐regulating the anti‐inflammatory cytokine IL‐10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.