盆底治疗仪联合重组人粒细胞集落刺激因子宫腔灌注对改善子宫内膜容受性的影响研究

［摘要］　目的　探讨盆底治疗仪联合重组人粒细胞集落刺激因子（G-CSF）宫腔灌注对改善子宫内膜容受性的影响。方法　选取2017-02～2018-07在广西贵港市人民医院生殖中心行体外受精(in-vitro fertilization,IVF)助孕的薄型子宫内膜患者60例,均以人工周期准备内膜后行冻融胚胎移植（frozen embryo transfer,FET）。按就诊顺序分为对照组（采用G-CSF宫腔灌注治疗）和观察组（采用G-CSF宫腔灌注联合盆底治疗仪治疗）,每组30例。比较两组治疗前后的的子宫内膜厚度（endometrial thickness,Em）、阻力指数（resistance index,RI）、A型子宫内膜率,治疗后的胚胎种植率、妊娠率。结果　治疗后,观察组Em值和A型子宫内膜率大于对照组,RI值低于对照组,差异有统计学意义（P<0.05）。胚胎种植率和妊娠率在治疗后两组比较差异无统计学意义（P>0.05）。结论　盆底功能障碍治疗仪结合G-CSF宫腔灌注可以改善薄型子宫内膜的容受性,增加Em。     

辅助生殖技术中薄型子宫内膜治疗的研究进展

［摘要］　薄型子宫内膜是指子宫内膜厚度低于能够获得妊娠的最低阈值,是评估子宫内膜容受性的重要指标。目前薄型子宫内膜的诊断标准尚未统一,对妊娠结局的影响尚不明确。该文对辅助生殖技术中薄型子宫内膜的治疗新进展作一综述。     

粒细胞集落刺激因子在急性心肌梗死治疗中的作用

急性心肌梗死是冠心病的一种严重类型，能够导致心肌细胞数量减少和心肌组织瘢痕形成，使心功能受损，发生心力衰竭，是目前心力衰竭的主要原因。近年来，许多研究发现粒细胞集落刺激因子（granulocyte—colony stimulating factor，G-CSF）具有促进心肌梗死后的组织修复和改善心功能的作用，为急性心肌梗死的治疗提供了又一新途径。国内外的动物实验和临床研究发现G-CSF可能通过多种机制影响心功能，现将其相关机制的研究综述如下。     

粒细胞集落刺激因子对心脏缺血—再灌注损伤大鼠心功能的影响

将32只Wistar大鼠在缺血—再灌注的复灌过程中分别灌入粒细胞集落刺激因子（G-CSF）0 ng/ml（I/R组）、10 ng/ml（G10组）、50 ng/ml（G50组）、300 ng/ml（G300组）,测定左心室收缩压（LVSP）、左心室舒张末压（LVEDP）、左心室内压上升最大速率（＋dp/dtmax）、左心室内压下降最大速率（-dp/dtmax）;用氯化三苯基四氮唑染色法检测心肌梗死面积。结果G10组的心功能指标（除LVEDP外）与I/R组相比无统计学差异（P〉0.05）;G50组LVSP高于I/R组,LVEDP低于I/R组（P〈0.05）;与I/R组相比,G300组LVSP、＋dp/dtmax和-dp/dtmax显著升高、LVEDP显著降低,G50组、G300组梗死面积百分比显著降低（P均〈0.01）。提示一定剂量的G-CSF可改善大鼠离体心脏的心功能,缩小心肌梗死面积。     

G-CSF不同处理方式对大鼠颈总动脉球囊损伤后内膜增生的影响

目的探讨粒细胞集落刺激因子（G-CSF）不同处理方式对大鼠颈总动脉球囊损伤后内膜增生以及再内皮化的影响,评价对损伤血管的影响。方法将雄性SD大鼠90只随机分为3组,每组30只,即G-CSF预处理组,于颈总动脉球囊损伤前7d开始皮下注射G-CSF,连续7d后,进行颈总动脉球囊导管损伤;G-CSF后处理组,于颈总动脉球囊损伤后即刻开始皮下注射G-CSF,连续7d;对照组:只进行颈总动脉球囊损伤。3组大鼠均于术后即刻,3,7,14,21及28d,取损伤血管段进行病理组织学检查观察细胞增殖的情况,并采用RT-PCR法检测内皮型一氧化氮合酶（eNOS）的表达。结果G-CSF预处理组内膜面积小于G-CSF后处理组及对照组,管腔直径多于对照组,内膜、中膜面积比值在3组中最低。G-CSF预处理组中eNOS的表达明显高于对照组（P<0.05）;G-CSF后处理组中eNOS的表达与对照组比较无明显差异;G-CSF预处理组与G-CSF后处理组比较亦无统计学差异。结论G-CSF可促进大鼠颈总动脉球囊损伤后再内皮化的进程,抑制内膜增生过程,对球囊损伤具有修复作用,可预防血管成形术术后的再狭窄,G-CSF预处理组较G-CSF后处理组的效果更佳。     

粒细胞集落刺激因子受体在急性髓性白血病骨髓CD34+细胞中的表达及其临床意义研究

目的 评价粒细胞集落刺激因子(G-CSF)应用于急性髓性白血病(AML)化疗患者的安全性.方法 对2008年3月至2009年1月天津医科大学总医院血液肿瘤科62例AML患者[初治或复发AML33例,完全缓解(CR)AML 29例]和16名正常人采用流式细胞术(FCM)和半定量逆转录一聚合酶链反应(RT-PCR)检测骨髓CD34+细胞G-CSFR的表达.结果 CD114+CD34+/CD34+比值在初治或复发组、CR组及对照组分别为(11.69±2.91)%、(31.84±8.62)%、(32.87±8.44)%(P<0.05),CR组和对照组比较差异无统计学意义(P>0.05).G.CSF受体mRNA表达在初治或复发组、CR组及对照组分别为(30.52±6.21)%、(85.13±21.25)%、(91.57±18.64)%(P<0.05),CR组和对照组比较差异无统计学意义(P>0.05).动态随访了13例AML患者,初治及CR时骨髓CD34+细胞上CD114+CD34+/CD34+比值分别为(12.58±2.00)%、(30.13±7.09)%,初治时低于CR时(P<0.05).G-CSF受体mRNA表达分别为(32.23±5.69)%、(83.27±19.79)%,初治组低于CR组(P<0.05).结论 G-CSF受体在AML患者骨髓CD34+细胞上的表达低于正常人CD34+细胞上的表达,故G-CSF用于治疗AML化疗后粒细胞缺乏期是安全的.     

免疫因素在子宫内膜异位症发病中的作用研究进展

子宫内膜异位症（EMs）是生育期妇女常见良性病,但具有侵袭、种植等特点,主要发生于盆腔、卵巢、直肠阴道隔等处,临床表现为痛经、慢性盆腔痛等,可引起不孕（〉50%）。目前EMs发病率逐年上升,但其发病机制尚不清楚。大量资料表明,免疫因素在EMs的发病机理中起重要作用,现将其研究进展综述如下。     

粒细胞集落刺激因子在急性心肌梗死治疗中的作用

急性心肌梗死（acute myocardial infarction．AMI）发病率、致残率和死亡率高,严重危害健康。由于成人体内心肌细胞缺乏再生能力,心肌梗死的坏死区将由结缔组织替代,梗死周围心肌重新排列重构心肌,并最终发展为心力衰竭。心力衰竭是AMI患者死亡的主要原因,目前治疗药物和介入疗法无法逆转已坏死的心肌细胞。     

自体富血小板血浆在慢性难愈合创面治疗中的应用进展

慢性难愈合创面俗称溃疡,是由于各种内外界因素引起的机体正常皮肤或组织缺损后,经过>4周的常规治疗干预,仍无法通过自身修复达到功能及解剖完整的创面。包括糖尿病足溃疡、下肢静脉性溃疡、压力性溃疡等,其发生机制复杂、病程长,具有很高的致残率。自体富血小板血浆（PRP）是高浓度血小板浓缩物,富含多种生长因子和纤维蛋白,可以促进创面修复和再生,加速软组织愈合,改善患者的愈合质量。近年研究发现,PRP在修复各种软组织缺损及促进愈合方面发挥重要作用。     

粒细胞集落刺激因子在缺血性脑卒中中的脑保护作用研究进展

粒细胞集落刺激因子（G CSF）是造血生长因子,主要用于各种原因引起的中性粒细胞减少症、骨髓移植等。近年来已有研究在动物实验中证实了 G CSF可缩小脑缺血再灌注动物模型的脑梗死体积,改善功能预后,其作用机制可能包括抗凋亡、抗炎症、促进神经和血管发生、诱导神经分化等。本文主要对 G CSF的信号传导途径及神经保护作用机制进行综述。     

重组人粒细胞集落刺激因子对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生的影响

目的 利用干细胞动员剂重组人粒细胞集落刺激因子(rhG-CSF)动员骨髓问充质干细胞(MSCs),探讨其对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生过程的影响.方法 制作颈动脉粥样硬化狭窄兔模型67只,分为rhG-CSF组(rhG-CSF+球囊损伤,n=35)和对照组(生理盐水+球囊损伤,n=32).以流式细胞仪检测外周血MSCs数量,苏木精咿红法染色观察损伤动脉形态,免疫组织化学检测增殖细胞核抗原(PCNA).结果 (1)rhG-CSF应用前,两组之间的外周血MSCs细胞数量差异无统计学意义.应用rhG-CSF后24 h外周血MSCs数量显著增加(P＜0.01),第7天达到高峰,14 d时仍明显增高;而对照组各个时间点MSCs数量差别均无统计学意义.(2)形态学观察显示,球囊损伤后1周,对照组内皮细胞仍然大片缺失,仪见少数新生的内皮细胞,而rhG-CSF组内皮细胞散在覆盖,新生内皮排列不规则.14 d时,对照组内皮覆盖面较小,基底层片状裸露,而rhG-CSF组内皮呈小片状覆盖.28 d时rhG-CSF组内皮间连接建立,细胞排列呈现方向性.(3)免疫组织化学检测显示,球囊损伤后,动脉中膜近血管腔侧可见少量PCNA阳性细胞,而新生内膜PCNA 阳性细胞最多.rhG-CSF组于7、14、28 d时,PCNA阳性细胞率(细胞增殖指数)均显著低于对照组(均P＜0.01).结论 rhG-CSF能有效地促进骨髓释放MSCs,提高外周血MSCs数量,并促进损伤动脉再内皮化,抑制新生内膜增生,改善血管重塑.     

重组人粒细胞集落刺激因子的免疫调节作用及其在肝衰竭中的应用

重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,G-CSF)最早被临床用于各种原因所致白细胞减少.目前的研究结果表明,G-CSF具有减轻多种毒物引起的肝脏病理损伤,促进肝细胞再生,并降低毒物致肝衰竭实验动物死亡率的作用[1-3].近期的临床试验结果显示,G-CSF对肝衰竭和酒精性脂肪肝患者具有治疗作用,且安全性良好,但机制尚不清楚[4-6].研究者普遍认为,G-CSF通过动员骨髓干/祖细胞至受损肝组织,与内源性机制相互作用促进肝脏再生[1,4].目前的研究还发现,G-CSF 具有特殊的免疫调节作用,揭示了其在促进再生外的另一可能作用机制——抗炎与免疫调节机制.     

集落刺激因子的生物学特性及在治疗上应用的研究进展

集落刺激因子(CSF)是一组糖蛋白物质,有刺激红系以外造血细胞增殖和分化的作用。目前已在广泛研究将CSF应用于治疗,主要作用有提高周围血细胞,降低细胞毒药物对骨髓的抑制,加速自体骨髓移植后的恢复,治疗艾滋病,诱导白血病细胞分化等。其副作用不多且较轻微。     

缺氧诱导因子在异位子宫内膜中的表达意义

目的探讨缺氧诱导因子-1α（HIF-1α）在子宫内膜异位症（EMT）发生、发展中的作用。方法采用免疫组化法检测36例EMT患者异位子宫内膜组织（观察组）中HIF-1α表达情况,并与26份正常子宫内膜组织（对照组）比较。结果观察组HIF-1α阳性表达率及强阳性表达率分别为66．67％、22．22％,对照组均为0,两组比较,P均〈0．05。结论HIF-1α在EMT发生、发展中起重要作用;缺氧可能是EMT发病的一个诱因。     

重组人粒细胞集落刺激因子对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生的影响

Objeelive To investigate the effect of rhG-CSF on mobilizing bone marrow-MSCs, reendothelialization and intima hyperplasia in carotid artery of rabbits post balloon catheter injury, nethods Rabbits were treated with rhG-CSF (25 μkg, twice daily, i. p, n =35) or saline (n =32) for 5 days, then, carotid arteries of rabbits were injured by balloon catheter. The number of peripheral MSCs was detected with FACS. The morphology of injuried artery was examined with hematoxylin and eosin stain, PCNA was determined with immunohistochemistry. Results (1) Number of peripheral MSCs was similar at baseline and significantly increased at 24 hours and peaked at 7 days and remained increased till 14 days post rhG-CSF. (2) Significant endothelial cell deletion was evidenced in the control group, while scatter endothelial cells was observed in the rhG-CSF group at 1 week post injury. Two weeks after injury, new endothelial area was significantly higher in rhG-CSF group compared to control group. At 4 weeks post injury, endothelial connection was evidenced and regularly displayed in rhG-CSF treated group. (3) PCNA-positive cells in the tunica intima were significantly lower in rhG-CSF treated rabbits at 7, 14 and 28 days compared that in control rabbits (all P ＜ 0.01). Conclusion rhG-CSF could mobilize the bone marrow-MSCs and promote re-endothelialization and attenuate intima hyperplasia post balloon catheter injury in carotid arteries of rabbits.     

重组人粒细胞集落刺激因子对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生的影响

Objeelive To investigate the effect of rhG-CSF on mobilizing bone marrow-MSCs, reendothelialization and intima hyperplasia in carotid artery of rabbits post balloon catheter injury, nethods Rabbits were treated with rhG-CSF (25 μkg, twice daily, i. p, n =35) or saline (n =32) for 5 days, then, carotid arteries of rabbits were injured by balloon catheter. The number of peripheral MSCs was detected with FACS. The morphology of injuried artery was examined with hematoxylin and eosin stain, PCNA was determined with immunohistochemistry. Results (1) Number of peripheral MSCs was similar at baseline and significantly increased at 24 hours and peaked at 7 days and remained increased till 14 days post rhG-CSF. (2) Significant endothelial cell deletion was evidenced in the control group, while scatter endothelial cells was observed in the rhG-CSF group at 1 week post injury. Two weeks after injury, new endothelial area was significantly higher in rhG-CSF group compared to control group. At 4 weeks post injury, endothelial connection was evidenced and regularly displayed in rhG-CSF treated group. (3) PCNA-positive cells in the tunica intima were significantly lower in rhG-CSF treated rabbits at 7, 14 and 28 days compared that in control rabbits (all P ＜ 0.01). Conclusion rhG-CSF could mobilize the bone marrow-MSCs and promote re-endothelialization and attenuate intima hyperplasia post balloon catheter injury in carotid arteries of rabbits.     

重组人粒细胞集落刺激因子对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生的影响

Objeelive To investigate the effect of rhG-CSF on mobilizing bone marrow-MSCs, reendothelialization and intima hyperplasia in carotid artery of rabbits post balloon catheter injury, nethods Rabbits were treated with rhG-CSF (25 μkg, twice daily, i. p, n =35) or saline (n =32) for 5 days, then, carotid arteries of rabbits were injured by balloon catheter. The number of peripheral MSCs was detected with FACS. The morphology of injuried artery was examined with hematoxylin and eosin stain, PCNA was determined with immunohistochemistry. Results (1) Number of peripheral MSCs was similar at baseline and significantly increased at 24 hours and peaked at 7 days and remained increased till 14 days post rhG-CSF. (2) Significant endothelial cell deletion was evidenced in the control group, while scatter endothelial cells was observed in the rhG-CSF group at 1 week post injury. Two weeks after injury, new endothelial area was significantly higher in rhG-CSF group compared to control group. At 4 weeks post injury, endothelial connection was evidenced and regularly displayed in rhG-CSF treated group. (3) PCNA-positive cells in the tunica intima were significantly lower in rhG-CSF treated rabbits at 7, 14 and 28 days compared that in control rabbits (all P ＜ 0.01). Conclusion rhG-CSF could mobilize the bone marrow-MSCs and promote re-endothelialization and attenuate intima hyperplasia post balloon catheter injury in carotid arteries of rabbits.     

重度宫腔粘连反复应用大剂量雌激素致子宫内膜非典型增生1例

患者女,33岁,主因“清宫术后闭经2个月”于2009年1月4日首次入院.2008年因原发不孕行试管婴儿妊娠双胎,孕5个月自然流产,流产后1周行清宫术.术后闭经,有周期性下腹痛.月经史16/3～4/35～40 d,经量中等,无痛经,G1P0.2002年曾行腹腔镜检查发现“盆腔子宫内膜异位症”.其母有胃癌病史.患者体质量指数22.1,妇科内诊无异常.经阴道B超:子宫内膜0.4 cm.宫腔镜检查:宫腔呈窄桶状,宫深5.5 cm,双侧输卵管开口未见,未见正常内膜.于2009年1月6日行宫腔镜宫腔粘连分离术(TCRA).术中打开宫腔,显露双侧输卵管开口,宫壁内膜薄,残余正常内膜面积小于1/3.术后给予戊酸雌二醇(补佳乐)10 mg/d,连续口服2个月余.     

重组人粒细胞集落刺激因子对兔颈动脉粥样硬化球囊损伤后再内皮化和内膜增生的影响

Objeelive To investigate the effect of rhG-CSF on mobilizing bone marrow-MSCs, reendothelialization and intima hyperplasia in carotid artery of rabbits post balloon catheter injury, nethods Rabbits were treated with rhG-CSF (25 μkg, twice daily, i. p, n =35) or saline (n =32) for 5 days, then, carotid arteries of rabbits were injured by balloon catheter. The number of peripheral MSCs was detected with FACS. The morphology of injuried artery was examined with hematoxylin and eosin stain, PCNA was determined with immunohistochemistry. Results (1) Number of peripheral MSCs was similar at baseline and significantly increased at 24 hours and peaked at 7 days and remained increased till 14 days post rhG-CSF. (2) Significant endothelial cell deletion was evidenced in the control group, while scatter endothelial cells was observed in the rhG-CSF group at 1 week post injury. Two weeks after injury, new endothelial area was significantly higher in rhG-CSF group compared to control group. At 4 weeks post injury, endothelial connection was evidenced and regularly displayed in rhG-CSF treated group. (3) PCNA-positive cells in the tunica intima were significantly lower in rhG-CSF treated rabbits at 7, 14 and 28 days compared that in control rabbits (all P ＜ 0.01). Conclusion rhG-CSF could mobilize the bone marrow-MSCs and promote re-endothelialization and attenuate intima hyperplasia post balloon catheter injury in carotid arteries of rabbits.