Effects of leukemia inhibitory factor on endogenous neural stem cell proliferation and glycoprotein-130 expression in a mouse model of cerebral infarction

Leukemia inhibitory factor （LIF） has been shown to promote proliferation of endogenous neural stem cells. In this study, we treated mice with cerebral infarction using LIF to investigate whether the LIF receptor subunit glycoprotein （gp）130 is involved in neuroprotection. After LIF treatment, the motor function of model mice was significantly improved. Immunofluorescence histochemistry showed increased numbers of endogenous neural stem cells surrounding the infarct foci. Western blot analysis revealed that gp130 expression was significantly decreased surrounding the infarcted foci. Results demonstrated that LIF promoted the proliferation of endogenous neural stem cells by inhibiting gp130 protein expression.

Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction

The present study established a mouse model of cerebral infarction by middle cerebral artery occlusion, and monitored the effect of 25 tJg/kg leukemia inhibitory factor and （or） basic fibroblast growth factor administration 2 hours after model establishment. Results showed that following administration, the number of endogenous neural stem cells in the infarct area significantly increased, malondialdehyde content in brain tissue homogenates significantly decreased, nitric oxide content, glutathione peroxidase and superoxide dismutase activity significantly elevated, and mouse motor function significantly improved as confirmed by the rotarod and bar grab tests. In particular, the effect of leukemia inhibitory factor in combination with basic fibroblast growth factor was the most significant. Results indicate that leukemia inhibitory factor and basic fibroblast growth factor can improve the microenvironment after cerebral infarction by altering free radical levels, improving the quantity of endogenous neural stem cells, and promoting neurological function of mice with cerebral infarction.

GATA3通过调控LIFR抑制人乳腺癌细胞的迁移能力

目的探究GATA结合蛋白3(GATA binding protein 3,GATA3)对乳腺癌细胞迁移能力的影响。方法在MCF7细胞中利用慢病毒载体介导的基因干涉技术敲低GATA3基因,使用实时定量荧光PCR(qRT-PCR)和蛋白质印迹检测GATA3和LIFR的mRNA和蛋白表达水平,Transwell实验检测MCF7细胞的迁移能力。在MCF7和T47D细胞中用染色质免疫沉淀(ChIP-qPCR)实验检测GATA3在LIFR的启动子区的结合位点。在敲低GATA3基因的MCF7细胞中回补LIFR,通过细胞划痕实验和Transwell实验检测MCF7细胞的迁移能力。结果与对照组相比,敲低GATA3基因的MCF7细胞的迁移能力增强(P_(均)<0.05)。与对照组相比,敲低GATA3基因的MCF7细胞的LIFR表达水平降低(P_(均)<0.05)。乳腺癌细胞MCF7与T47D中GATA3在LIFR的启动子区有结合(P_(均)<0.05)。在敲低GATA3基因的MCF7细胞中稳定过表达LIFR可以部分挽救GATA3基因敲低引起的细胞迁移能力的增强(P_(均)<0.05)。结论GATA3通过转录激活LIFR抑制乳腺癌细胞MCF7的迁移。

LIF调控奶牛子宫内膜上皮细胞容受性基因表达研究

接受态的子宫内膜对于奶牛胚胎的成功植入至关重要。为探讨白血病抑制因子(LIF)对奶牛子宫内膜容受性的调控机制,试验将奶牛子宫内膜上皮细胞分为对照组、LIF处理组、LIF+STAT3共处理组,研究了LIF对子宫内膜容受性的作用和STAT3信号通路对奶牛子宫内膜容受性的调控。采用实时荧光定量RT-PCR和Western blot检测容受性相关基因HOXa10、VEGF和炎症相关基因TLR4、NF-κB的mRNA和蛋白表达变化。结果表明:与对照组相比,LIF处理组奶牛子宫内膜上皮细胞的容受性相关基因HOXa10、VEGF的表达量显著增加(P<0.05),炎症相关基因TLR4、NF-κB的表达量显著增加(P<0.05)。LIF+STAT3共处理组的HOXa10、VEGF的表达量与LIF处理组比较显著降低(P<0.05),与对照组无显著差异(P>0.05);TLR4、NF-κB的表达量与LIF处理组比较无显著差异(P>0.05),显著高于对照组(P<0.05)。说明LIF通过激活STAT3信号通路调控子宫内膜上皮细胞HOXa10、VEGF的表达,能够增强子宫内膜的容受性。

Spatiotemporal expression of leukemia inhibitory factor receptor protein during neural tube development in embryos with neural tube defects

Leukemia inhibitory factor receptor(LIFR),as a neuroregulatory cytokine receptor,generally shows a neuroprotective effect in central nervous system injuries.In this study,to understand the effect of LIFR on pathogenesis of neural tube defects,we explored spatiotemporal expression of LIFR at different stages of fetal development in normal and neural tube defect embryos.Spina bifida aperta was induced with all-trans retinoic acid on embryonic day 10 in rats,and the spatiotemporal expression of LIFR was investigated in spina bifida aperta rats and healthy rats from embryonic day 11 to 17.Real time-polymerase chain reaction and western blot assay were used to examine mRNA and protein expression of LIFR in healthy control and neural tube defect embryos.Results of the animal experiment demonstrated that expression of LIFR protein and mRNA in the spinal cords of normal rat embryos increased with embryonic development.LIFR was significantly downregulated in the spinal cords of spina bifida aperta rats compared with healthy rats from embryonic days 11 to 17.Immunohistochemical staining showed that the expression of LIFR in placenta and spinal cord in spina bifida aperta rat embryos was decreased compared with that in control embryos at embryonic day 15.Results from human embryo specimens showed that LIFR mRNA expression was significantly down-regulated in spinal cords of human fetuses with neural tube defects compared with normal controls at a gestational age of 24 to 33 weeks.The results were consistent with the down-regulation of LIFR in the animal experiments.Our study revealed spatiotemporal changes in expression of LIFR during embryonic neurulation.Thus,LIFR might play a specific role in neural tube development.All animal and human experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University,China(approval No.2016PS106K)on February 25,2016.

Leukemia Inhibitory Factor Decreases Neurogenesis and Angiogenesis in a Rat Model of Intracerebral Hemorrhage

Neurogenesis and angiogenesis can improve the neurologic function after intracerebral hemorrhage(ICH).Leukemia inhibitory factor(LIF)plays an important role in neurogenesis and angiogenesis.In this study,a rat model of autologous blood-induced ICH was used to evaluate the effect of LIF on the neurogenesis and angiogenesis following ICH.After ICH,LIF-positive neurons and dilated vessels were detected in the peri-hematomal region.It was found that LIF levels increased significantly and peaked 14 days after ICH induction.Double immunofluorescence confirmed that LIF was expressed in neurons and endothelial cells.ICH also led to increases of doublecortin(DCX)-and von Willebrand factor(vWF)-positive cells as well as proliferation of cell nuclear antigen(PCNA)+/DCX+and PCNA+/vWF+nuclei.All these ICH-induced increases were significantly attenuated by exogenous LIF in fusion.These data suggested that LIF was a negative regulator of neurogenesis and angiogenesis after ICH.

Expression of Leukemia Inhibitory Factor in Airway Epithelial Tissue of Asthmatic Rats

In order to investigate the expression of leukemia inhibitory factor （LIF） in airway epithelial tissues of normal and asthmatic rats, the influence of dexamethasone and the role of LIF in pathogenesis of asthma, 30 Sprague-Dawley （SD） rats were randomly divided into 3 groups （10 for each group）： normal group, asthma model group, and dexamethasone-interfered group. In asthma model group and dexamethasone-interfered group, asthma rat models were established by intraperitoneal （i.p.） injection of 10% ovalbumin （OVA） and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone （2 mg/kg, i.p） 30 min before each challenge. The expression of LIF protein in lung was detected by immunohistochemistry. The results showed that LIF protein was mainly expressed in cytoplasm of bronchial epithelial cells. The expression of LIF protein in the airway epithelial tissue of asthma model group was significantly higher than that in normal group and dexamethasone-interfered group （P〈0.01）, but there was no significant difference between normal group and dexamethasone-interfered group （P〉0.05）. It was concluded that the expression of LIF was increased significantly in the airway epithelial tissue of the asthma rats, and dexamethasone could down-regulate the expression of LIF. It was suggested that LIF might play an important role in the pathogenesis of asthma as an inflammation regulator.

LIF/LIFR/STAT3通路在多囊卵巢综合征大鼠的子宫内膜容受性中的作用

目的探讨白血病抑制因子/白血病抑制因子受体/信号转导和转录激活因子3(LIF/LIFR/STAT3)通路在多囊卵巢综合征(polycystic ovarian syndrome,PCOS)大鼠的子宫内膜容受性中的作用。方法将40只21日龄SD雌性大鼠平均分为正常(control)组、模型(model)组、假手术(sham-operation)组及LIF组,每组10只。颈后皮下注射硫酸普拉睾酮钠用于建造PCOS大鼠模型。检测每组大鼠血清中睾酮(T)、葡萄糖和胰岛素水平;HE染色观察各组大鼠子宫形态及内膜变化;免疫组化、Western blotting及实时荧光定量PCR(qRT-PCR)测定大鼠子宫内膜中LIF及STAT3的蛋白及mRNA表达,用Mann Whitney-U检验或t检验统计分析。结果与control组相比,PCOS大鼠的整合素avb3、血清T、胰岛素及葡萄糖水平明显升高(P=0.000,P=0.000,P=0.000,P=0.001),补充外源性LIF可明显降低PCOS大鼠的整合素avb3、血清T、葡萄糖及胰岛素水平(P=0.000,P=0.002,P=0.003,P=0.007)。HE结果显示,外源性LIF可改善PCOS大鼠的宫腔及腺体形态,并可增加大鼠子宫腺体及腺腔的等效直径(P=0.000,P=0.000)和面积(P=0.000,P=0.000)、腺间质面积比(P=0.000)及子宫内膜平均厚度(P=0.006),差异具有统计学意义。免疫组化、Western blotting及qRT-PCR结果显示,与control组相比,model组中LIF及p-STAT3蛋白及mRNA表达明显降低;与model组比较,LIF组中LIF及p-STAT3蛋白及mRNA表达明显升高,差异具有统计学意义(P<0.05)。结论外源性补充LIF可改善PCOS大鼠的子宫内膜容受性,其作用机制与LIF/LIFR/STAT3通路有关。

藏西北绒山羊子宫内膜容受性相关基因和可变剪接事件的综合分析

背景:藏西北绒山羊子宫内膜容受性是胚胎植入的关键因素,目前对于藏西北绒山羊子宫内膜容受性相关基因表达及可变剪接的认识还未明确。目的:分析并挖掘藏西北绒山羊子宫内膜容受性相关的基因和可变剪接事件。方法:在妊娠第5天和第15天(分别代表容受前子宫内膜组和容受性子宫内膜组),分别随机选取3只藏西北绒山羊,采集子宫内膜组织,苏木精-伊红染色观察组织形态,免疫组织化学检测子宫内膜容受性标志蛋白白血病抑制因子、血管内皮生长因子的表达水平;提取子宫内膜组织总RNA,质量检测合格后进行转录组测序,寻找差异表达的mRNA、长链非编码RNA、环状RNA和miRNA,进行功能预测,并分析与子宫内膜容受性相关的可变剪接mRNA和长链非编码RNA。结果与结论:(1)与容受前子宫内膜组比较,容受性子宫内膜组子宫内膜组织中白血病抑制因子和血管内皮生长因子蛋白的表达水平明显升高;(2)测序结果显示,差异表达基因多为mRNA和长链非编码RNA,包括250个上调的mRNA、193个上调的长链非编码RNA、135个下调的mRNA和123个下调的长链非编码RNA,显著富集于Wnt、Hedgehog和Hippo信号通路;(3)可变剪接事件分析显示有8个差异表达的可变剪接转录本,均为mRNA分子,其中2个下调、6个上调,与血管内皮生长因子受体信号、细胞运动和胚胎发育有关。

参芪地黄汤化裁联合胰岛素治疗二甲双胍控制血糖不佳气阴两虚证糖尿病的效果

目的探讨参芪地黄汤化裁联合胰岛素治疗在二甲双胍控制血糖不佳气阴两虚证糖尿病患者中的应用价值。方法选取2019年3月—2022年6月就诊的100例二甲双胍控制血糖不佳气阴两虚证糖尿病开展回顾性研究,均为2型糖尿病。根据治疗方法不同分为研究组和常规组,每组50例。研究组采用参芪地黄汤化裁联合胰岛素治疗,常规组采用胰岛素治疗。比较2组疗效、中医证候积分、血糖相关指标[糖化血红蛋白(HbA1c)、稳态模型胰岛素抵抗指数(HOMA-IR)、餐后2 h血糖(2 h PBG)、空腹血糖(FBG)、胰岛β细胞功能指数(HOMA-β)]、炎性指标[C反应蛋白(CRP)、单核细胞趋化蛋白-1(MCP-1)、白血病抑制因子(LIF)、高迁移率族蛋白B1(HMGB1)]、预后指标[脂蛋白相关磷脂酶A2(Lp-PLA2)、血尿酸(SUA)、甲状腺球蛋白(TG)]及安全性。结果研究组临床总有效率94.00%(47/50)高于常规组80.00%(40/50)(P<0.05)。治疗后研究组各中医证候积分及总积分低于常规组(P<0.05)。治疗后研究组HbA1c、2 h PBG、FBG、HOMA-IR低于常规组,HOMA-β高于常规组(P<0.05)。治疗后研究组CRP、MCP-1、LIF、HMGB1、Lp-PLA2、SUA、TG低于常规组(P<0.05)。2组不良反应发生率比较差异无统计学意义(P>0.05)。结论参芪地黄汤化裁联合胰岛素治疗二甲双胍控制血糖不佳气阴两虚证糖尿病患者效果显著,可有效降低血糖水平,改善临床症状,减轻炎症反应,且安全性高。

卵泡液中白血病抑制因子(LIF)和血清中E2在早期胚胎发育中的作用

目的:阐述卵泡液中白血病抑制因子(LIF)和血清中E2在早期胚胎发育中的作用。方法:利用临床62例控制性超促排卵(COH)IVF-ET患者治疗过程中测定的血清E2数据和取卵时收集到的卵泡液,采用ELISA法测定卵泡液中LIF含量,分析LIF在取卵日不同E2组中的差异,并进一步分析其在卵母细胞、胚胎发育中的作用。结果:LIF在E2=1500-4000pg/ml组最高,在E2<1500pg/ml组中表达最低;在不同年龄组表达无差异。LIF<15pmol/L和≥15pmol/L组间受精率、可用胚胎率均存在显著性差异。LIF浓度与受精率、可用胚胎率成正相关。结论:受精率及早期胚胎的质量可能与卵泡液中LIF含量有关。卵泡液中LIF的浓度受周围血E2的影响;合适的E2浓度有利于卵泡液中LIF的提高。

妊娠小鼠子宫内膜LIF基因表达的研究

本文对妊娠第4天(Ⅰ组)、第7天(Ⅱ组)、第10天(Ⅲ组)的小鼠(各20只)子宫内膜LIF基因表达进行了研究。Ⅰ组20只小鼠子宫内膜全部存在LIF基因的表达、Ⅱ组有5只小鼠表达、Ⅲ组仅有1只小鼠表达。文中对不同孕期LIF基因的表达程度与胚胎着床的关系进行了讨论。

小鼠子宫内膜LIF基因表达与雌、孕激素的关系

白血病抑制因子(LIF)是一种多功能活性的糖蛋白,LIF基因在大多数妊娠第4天的小鼠子宫内膜进行着强烈的表达,然而LIF基因表达调控的机制目前尚不清楚。本实验对168只妊娠第4～5天的小鼠LIF基因表达和血清中雌、孕激素水平分别进行了检测,发现18只小鼠无LIF基因表达,其血清中雌、孕激素水平分别极显著(P<0.01)和显著(0.01<P<0.05)低于其他表达的小鼠。提示:雌、孕激素对小鼠LIF基因表达过程中起着一定的作用,将为LIF基因表达调控机制的深入研究打下基础。

GDNF和LIF对小鼠精原干细胞体外增殖的影响

【目的】探讨胶质细胞源性神经营养因子(GDNF)和白血病抑制因子(LIF)对小鼠精原干细胞(SSCs)体外增殖的影响,为后续SSCs的诱导分化、转基因动物生产、基因治疗等研究奠定基础。【方法】收集6～8日龄小鼠睾丸,采用机械法和2步酶消化法获得细胞悬液。通过多次差异贴壁法分离纯化SSCs和支持细胞,采用碱性磷酸酶(AP)染色和RT-PCR检测Ngn3和Oct4基因2种方法对SSCs进行鉴定。采用单独添加GDNF(添加量为0,10,20,40ng/mL)或LIF(添加量为0,500,1 000,1 500U/mL)的无血清DMEM/F12培养基培养SSCs,于培养第3,5,7天取样,同时用添加GDNF和LIF(各因子单独添加量两两组合)的无血清DMEM/F12培养基培养SSCs,于培养第3,4,5天取样,采用甲基噻唑基四唑(MTT)法检测GDNF、LIF对SSCs体外增殖的单因子效应和配伍效应。【结果】与对照组相比,不论培养时间如何,单独添加20和40ng/mL的GDNF可以显著促进SSCs增殖(P<0.05),而单独添加不同量LIF对SSCs增殖的影响不显著(P>0.05);同时添加20ng/mL GDNF和1 000U/mL LIF可以显著促进SSCs的增殖,在该条件下当精原干细胞接种密度为(6×104)～(10×104)mL-1,共培养5d时,其OD490值为0.696。【结论】DMEM/F12培养基中单独添加20ng/mL GDNF或同时添加20ng/mL GDNF和1 000U/mL LIF可以显著促进小鼠SSCs的体外增殖。

习惯性流产胚胎绒毛细胞LIF基因的表达

本文采用RT-PCR技术对25例习惯性流产胚胎绒毛细胞和25例正常妊娠的人工流产绒毛细胞LIF基因表达进行了研究，以探讨胚胎绒毛组织LIF基因表达与流产之病因的关系。结果发现在流产组中，有5例（占20%）流产胚胎绒毛组织无LIF基因表达，而正常组绒毛组织中均检测到LIF基因表达，两组经统计学处理具有显著性差异（P＜0.01）。本研究结果提示胚胎绒毛组织LIF基因表达缺陷可能是造成流产的原因之一。

外源性LIF和IL-1对围着床期小鼠子宫内膜整合素β_3亚基表达的调节

Objective:To study regulation of external leukemia inhibitory factor(LIF) and interlukin 1(IL 1) on the expression of integrin β 3 in the mouse endometrium during peri implantation period and explore the mechanism which LIF participate in embryonic implantation.Methods:The mice were injected peritoneally with LIF,IL 1 or IL 1ra at different administration on day 2～4 of pregnancy.The level of integrin β 3 protein was measured with Westernblot method and mRNA measured with RT PCR.Results:The levels of integrin β 3 protein and mRNA were increased by LIF and IL 1(P<0.05) and which relied on administration.The level of integrin β 3 mRNA was decreased by IL 1ra (P<0.05).Conclusion:LIF and IL 1 of cytokines can improve the expression of integrin β 3 in the peri implantation endometrium of mouse.Both of them may take part in implantation by regulating cell adhesion molecules.

LIF及其抗体对小鼠胚胎着床影响的体外研究

目的 :研究外源性白血病抑制因子 (LIF)及其抗体对小鼠胚胎着床的影响。方法 :将妊娠 4d的小鼠胚胎种植于已建立的子宫内膜体外模型上 ,观察不同浓度的LIF及其抗体对小鼠胚胎的粘附、植入及扩展情况。并用RT PCR法测定子宫内膜上皮细胞整合素β3的变化。结果 :不同浓度的LIF促进了胚胎的粘附 (P <0 .0 5 ) ,胚胎的扩展率降低。加入LIF抗体 (5 ,1 0 μg/ml)降低了胚胎的粘附率 (P <0 .0 5 ) ,同时LIF对整合素β3的表达有明显的促进作用 (P <0 .0 1 ) ,加入抗体后整合素β3的表达降低。结论

LIF对人胎脑神经干细胞体外增殖和分化的影响

目的:观察白血病抑制因子(LIF)对体外培养的人胎脑神经干细胞增殖和分化的影响。方法:用添加表皮生长因子(EGF)和碱性成纤维细胞生长因子(FGF2)的N2培养基培养人神经干细胞(hNSC)。实验分添加LIF(LIF+)组和无LIF(LIF-)组,接种12天后计数细胞集落(球)的形成率。传代培养观察120天,定期进行活细胞计数,绘制生长速率曲线。取第6代细胞球进行分化诱导,免疫荧光技术鉴别神经细胞的特异性抗原标志,并计算各细胞类型间的比例。结果:两组集落形成百分比分别为:LIF+为0.50%-0.91%;LIF-为0.49%-0.94%。两组间的差异并无显著意义(P>0.05)。在相同培养条件下,各例胎脑来源的NSC扩增速率的相差并无显著性意义(P>0.05),但LIF对NSC扩增有重要作用,刺激细胞扩增了约4000-8400倍,无分化发生;LIF-组仅为43-97倍,培养两个月后可观察到分化现象。在培养过程中观察到:LIF的作用主要表现在细胞接种传代约50-60天以后。用免疫细胞化学荧光进行分化细胞类型鉴定,计数神经元和星形胶细胞数,并计算其中神经元所占的百分比。LIF+培养为12%-83%,明显高于LIF-组的8%-23%(P<0.005),来源于海马的NSC分化为神经元的比例要高于来源于纹状体的NSC。结论:LIF能阻抑人胎脑NSC的分化,促进其体外长期增殖,其效应主要表现在接种传代培养的50-60天以后。LIF还影响NSC的分化,可显著提高分化细胞中神经元的百分比,海马源性hNSC对LIF更为敏感。

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

二补助育改良方对小鼠子宫内膜胞饮突、LIF、ER和PR表达的影响

目的观察二补助育改良方对胚泡着床障碍模型小鼠子宫内膜胞饮突、白血病抑制因子(leukemia inhibitory factor,LIF)、雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)表达的影响。方法建立小鼠胚泡着床障碍模型,将50只实验动物分为5组:空白组、模型组、西药组1(补佳乐组)、西药组2(阿司匹林组)、二补助育改良方组,每组10只。造模与给药同时进行,其后处死小鼠,扫描电镜观察胞饮突的表达,并采用免疫组化HBP法检测小鼠子宫内膜LIF、ER、PR的表达量。结果扫描电镜下,二补助育改良方组小鼠子宫内膜表面形态较规整,大量微绒毛及丰富胞饮突表达,细胞之间的间隙明显。免疫组化结果示,二补助育改良方组小鼠子宫内膜LIF、ER、PR表达较模型组明显增加(P<0.05);LIF表达低于补佳乐组(P<0.05),ER表达优于补佳乐组(P<0.05),PR表达与补佳乐组无明显差异(P>0.05);各指标与阿司匹林组比较无明显差异(P>0.05)。结论二补助育改良方可能通过调节胚泡着床期子宫内膜胞饮突、LIF、ER和PR的表达,从而提高子宫内膜容受性,参与胚泡植入的黏附过程,改善着床障碍,创造良好的受孕环境,促进胚泡着床。