重组人白细胞介素3对环磷酰胺所致犬造血损伤的治疗作用

白细胞介素3(interleukin-3,IL-3)又称多集落刺激因子(multi-colony stimulating factor),是作用于较早期阶段的具有广谱效应的造血刺激因子,对恶性贫血、再生障碍性贫血、骨髓增生异常综合征(MDS)以及各种继发性造血功能障碍疾病有显著疗效。本实验建立环磷酸胺(Cy)致家犬造血抑制的动物模型,用rhIL-3和碳酸锂(LC)进行对比研究,阐明rhIL-3的疗效、作用机理及毒副作用,为进一步研制和应用IL-3提供依据。     

重组人白细胞介素11对小鼠巨核细胞生成的促进作用

应用干细胞培养及集落形成法观察到白细胞介素11(IL-11)虽不能单独使小鼠骨髓细胞形成集落,但和白细胞介素3(IL-3)合用时,对正常及5-FU处理后小鼠骨髓细胞的集落形成有明显的促进作用,其中含巨核细胞的集落(CFI-GMM CFU-M)数较IL-3单独组分别增加约2.5和7倍。巨核细胞的体积测量法显示IL-11可增大成熟巨核细胞的体积。复种实验表明巨核细胞的早期集落形成受IL-3的刺激,而进一步分化和增殖需要IL-11的参与。在干细胞因子(SCF)的协同下,IL-11可使5-FU处理后小鼠骨髓细胞形成多量的未分化集落(CFU-Blast),提示IL-11在造血干细胞早期的自我更新中可能起着重要的作用。     

白细胞介素3与白细胞介素6基因疗法对化疗造血损伤的恢复作用

为观察白细胞介素（ＩＬ）－３、ＩＬ－６基因疗法对化疗后造血恢复及重建的作用，研究了成纤维细胞介导的ＩＬ－３、ＩＬ－６基因疗法以及合用两种基因疗法对５－氟尿嘧啶所造成的造血损伤小鼠模型的恢复作用。结果发现，单用ＩＬ－３基因疗法对化疗后小鼠中性粒细胞及白细胞减少具有促恢复作用，但对血小板促恢复作用不明显；单用ＩＬ－６基因疗法对化疗后小鼠血小板及中性粒细胞减少具有促恢复作用；当合用ＩＬ－３、ＩＬ－６基因疗法时可使化疗后小鼠血小板、中性粒细胞及白细胞提前恢复到化疗前水平，尤其血小板恢复作用更明显，且最低水平时血小板和中性粒细胞数量高于单一疗法时的数量，但合用对白细胞恢复作用效果与单用ＩＬ－３基因疗法相比无显著差异。对小鼠骨髓ＣＦＵ－ＧＭ及ＣＦＵ－ＭＫ进行体外动态观察，发现合用疗法促进ＣＦＵ－ＧＭ、ＣＦＵ－ＭＫ恢复作用显著高于单一疗法。结果表明合用ＩＬ－３、ＩＬ－６基因疗法能显著恢复化疗导致的造血损伤，促进化疗后血细胞恢复的疗效显著优于单用ＩＬ－３或ＩＬ－６基因疗法，可望为恢复肿瘤患者放、化疗导致的机体造血损伤提供新的途径。     

IL—6基因转染的骨髓基质细胞系对骨髓移植小鼠造血功能恢复？…

目的：探讨白细胞介素６（ＩＬ－６）基因转染的骨髓基质细胞系ＱＸＭＳＣ１ＩＬ－６对骨髓移植后造血功能的重建作用。方法：将骨髓造血细胞和骨髓基质细胞系一起经尾静脉注射给同系小鼠，建立骨髓移植（ＢＭＴ）模型。小鼠的造血功能用脾结节（ＣＦＵ－Ｓ）、粒－单系祖细胞（ＣＦＵ－ＧＭ）、红系祖细胞（ＣＦＵ－Ｅ、ＢＦＵ－Ｅ）测定及外周血各项血液学指标来确定。结果：ＷＸＭＳＣ１ＩＬ－６转基因骨髓基质细胞可明显增强ＢＭ     

重组人白细胞介素1β对急性照射小鼠造血系统的保护作用

重组人白细胞介素１β对急性照射小鼠造血系统的保护作用谭筱江邬梦麒凌世淦恶性肿瘤患者在进行照射的同时，常伴有不同程度的骨髓抑制，导致粒细胞、血小板缺乏及贫血，严重者可致患者死亡。近年来，国内外学者研究发现重组人白细胞介素１β（ｒｈＩＬ－１β）能促进造血...     

小鼠静脉内注射白细胞介素8对动员骨髓造血干／祖细胞的作用研究

研究重组人白细胞介素８动员小鼠造血干／祖细胞的生物学效应。方法：将ｒｈＩＬ－８单独或联合重组人粒细胞集落刺激因子给ＢＡＬＢ／ｃ小鼠静脉内注射，观察ＢＡＬＢ／ｃ小鼠外周血单个核细胞的增殖能力；并将ＰＢＭＮＣ回转给经致死性照射的ＢＡＬＢ／ｃ小鼠，观察其造血重建功能。     

白细胞介素6与造血调控

ＩＬ－６是一种造血刺激因子。多种血细胞和肿瘤细胞均可产生和分泌ＩＬ－６。它能促进造血细胞的生成，并与ＩＬ－３、ＳＣＦ等多种细胞因子具有协同作用。对某些白血病细胞具有生长调节和诱导分化作用，与ＭＭ的发生与发展有密切相关性。     

白细胞介素—11与造血调控

白细胞介素－１１（ＩＬ－１１）是源于骨髓基质细胞的造血生长因子家族中又一新的成员，具有多种生物学活性，在造血调控中起着重要调节作用。本文就ＩＬ－１１的发现与命名、基因结构、生物学活性和ＩＬ－１１受体作一综述。     

EFFECT OF rhIL-6 ON EARLY HEMATOPOIETIC RECOVERY IN IRRADIATED MICE

The effect of recombinant human interleukin-6 ( rhIL-6) on the early phase of post-irradiation hematopoietic recovery ( mainly CFU-S, CFU-GM and CFU-E) has been studies in 6.5 Gy gamma-irradiated C57BL / 6J mice, which had been given subcutaneous injection of rhIL-6 b. i. d. at 10, 100, 200, 500 and 1 000μg/kg/d for 4 or 6 consecutive days started from 30 min after irradiation. It was shown that the effect of IL-6 on the early phase of post-irradiation hematopoietic recovery is dose-dependent and diphasic. At the doses of 200-1000μ/kg/d, IL-6 had a favorable effect on post-irradiation hematopoietic recovery expressed as increse of spleen weight and CFU-S, and elevation of CFU-GM yield and total CFU-GM content in femur. Administration of relatively low doses of IL-6(10-100 μg/kg/d) suppressed postirradiation hematopoietic regeneration. High a dose (1 000μg/kg/d) did not show any stronger stimulative effect on post-irradiation hematopoietic reconstitution. There is an optimal range of IL-6 dose for tr     

EFFECT OF RECOMBINANT MOUSE INTERLEUKIN-3 ON HEMATOPOIESIS IN NORMAL AND CYCLOPHOSPHAMIDE-TREATED MICE

Intraperitoneal injection of recombinant mouse IL-3 in normal mice for 6 days did not induce any significant changes in leukocyte and neutrophil counts. In comparison with saline controls, IL-3-treated mice experienced a 1.7-fold increase of bone marrow nucleated cells and 3.6-fold increase of CFU-GM colonies. Tritium thymidine incorporation of bone marrow cells significantly increased in IL-3-treated mice as compared with that in normal saline-treated mice. These results suggested that IL-3 expanded the number of granulocyte-macrophage progenitor cells but not the peripheral neutrophils. We examined the effect of IL-3 on hematopoietic reconstitution in a cyclophosphamide-treated mouse model. We found that the absolute neutrophil number of mice treated with IL-3 increased significantly on day 6 post injection when compared with the control mice (6.2± 4.1×109 / L versus 0.98± 1.4 × 109/ L, P<0.01) . The results demonstrated that IL-3 stimulated an early recovery of neutrophils after cyclophosphamide-i     

rhIL-12对恒河猴造血系统辐射防护作用的初步研究

摘要本研究旨在初步观察重组人白介素-12（rhIL-12）对急性辐射损伤猴造血系统的防护和治疗作用,为同类型病人的临床救治提供实验依据。在体外实验中,观察了不同浓度rhIL-12（0、1、5、25、125和625ng/ml）对来自人和健康成年猴骨髓造血祖细胞集落形成能力的影响。在体内实验中,用11只经3．0Gy全身照射后90d活存猴再经致死剂量^60Coγ（6．0Gy）射线全身1次照射以建立重度骨髓型急性放射病动物模型。模型动物被随机分为照射对照组（n=4）、单次给药组（n=3）和分次给药组（n=4）。单次给药组于照射后2h皮下注射rhIL-124μg／kg,分次给药组分别于照射后2h和3、6、9d皮下注射rhIL-121μg/kg,对照组于皮下注射同样体积的PBS。观察照射后动物活存情况和外周血象变化。体外培养结果显示,不同浓度rhIL-12可明显促进正常猴和人骨髓单个核细胞形成各系造血祖细胞集落,特别是CFU-E和CFU-GM最为明显。照射对照组动物于照射后22d内全部死亡,死亡动物平均活存时间为（20．3±1．2）d;rhIL-12单次给药组3只动物全部存活,rhIL-12分次给药组1只动物于照射后17d因贫血死亡。与对照组比较,rhIL-12治疗能明显提高动物存活（P=0．018）,并促进外周血白细胞数、血红蛋白水平、血小板以及网织红细胞数的恢复（P〈0．05）。结论：rhIL-12可明显促进灵长类骨髓造血祖细胞体外集落形成,并明显促进重度骨髓型急性放射病猴的造血功能恢复,提高动物存活率。     

小鼠淋巴结基质细胞特性及其在辐射损伤修复中的作用

不论是体外器官培养,还是液体单层细胞培养,基质细胞都是在实质细胞退化死亡基础上不断增殖。单层培养时可观察到多角形及纺锤形细胞散在分布,也可形成集落或单层。器官培养时可形成“滋养细胞”等。在淋巴结基质细胞上可见有造血免疫细胞生长,说明在培养条件下基质细胞可支持实质细胞的生长。0.75Gy照射后,基质细胞(合基质祖细胞)与未照射组对比没有减少,甚至有所增加,而1.5Gy、4.0Gy和8.0Gy照射后其数量显著下降。淋巴结基质祖细胞的D_0值是2.7Gy,n值是1.5     

人脐血细胞在SCID小鼠体内生长特性的研究

本实验将人脐血和骨髓单个核细胞,分别经腹腔输入C.B-17SCID小鼠体内,动态观察了受体内人CD3抗原表达及增殖能力。结果输入脐血或骨髓单个核细胞后,受体内均有逐渐增加的人CD3细胞(分别从2.0％、1.5％增至6.8％、5.4％),且脐血组高于骨髓组。接种后60d,二组实验小鼠骨髓CFU-GM产率明显高于对照组(P<0.01),脐血组高于骨髓组(P<0.05)。在60d时受体小鼠外周血、骨髓、肝、脾、肺组织和骨髓CFU-GM集落,用PCR方法检测出人Y染色体特异DNA片段。结果表明,输注人脐血或骨髓细胞到SCID小鼠腹腔后,可在体内长期生长且具有增殖能力。这种模型的建立为今后造血细胞体内研究提供了一种良好途径,也进一步以动物实验证实脐血造血干/祖细胞具有不同于骨髓造血细胞的生物学特性。     

STUDIES ON THE RECOVERY OF THE IMMUNE RESPONSE IN IRRADIATED MICE THYMECTOMIZED IN ADULT LIFE

Experiments performed on CBA mice thymectomized in adult life, exposed to lethal doses of irradiation and given tissue therapy are described. Marrow, foetal liver, or spleen cells from syngeneic donors could protect the mice against the lethal effects of irradiation. Between 30 and 70 days' postirradiation, however, marrow-treated, thymectomized irradiated mice showed evidence of trophic disturbances, such as failure to gain weight, in contrast to sham-operated, irradiated, marrow-treated controls. The immune responses of experimental and control mice were tested up to 150 days' postirradiation by challenging with sheep erythrocytes and allogeneic skin grafts. Sham-operated irradiated controls, whether protected with marrow, foetal liver, or spleen cells, produced normal immune responses when challenged at 28, 60, or 150 days after irradiation. Neither foetal liver cells nor marrow cells, in doses of up to 40 million cells per mouse, enabled thymectomized irradiated mice to recover normal immune functions. Spleen cells, from normal donors but not from neonatally thymectomized donors, restored immunological capacity in such mice. It is concluded that immunologically competent cells are present in the spleen of normal adult donors and can function in the absence of the thymus. Bone marrow, on the other hand, does not contain an adequate population of such cells but has lymphoid precursor cells, the descendants of which can become immunologically competent only in the presence of a functioning thymus mechanism.     

THE EFFECT OF EPITHELIAL REMNANT AND WHOLE ORGAN GRAFTS OF THYMUS ON THE RECOVERY OF THYMECTOMIZED IRRADIATED MICE

Work has been presented which suggests that thymus epithelial reticular cells are not effective in restoring the microscopic morphology of lymphoid tissues and their immunologic capacities. They function in recruiting precursors of thymus lymphocytes from the host animals to produce an organ which, after it becomes architecturally normal, can reconstitute the defective host. Intact thymus grafts in situ from 10–14 days, but not for shorter periods of time, have been shown to result in a return toward normal of these two parameters. Evidence is offered to show that few dividing cellular components in the lymphoid tissue originate from the thymus remnant grafts, and that a minor cellular component is contributed by the intact grafts. These data support the concept that the structural and functional development of the lymphatic tissue in thymectomized animals is dependent on thymus lymphoid cells and/or their products, and that the epithelial-reticular cells do not have a direct action in peripheral lymphoid reconstitution.     

MSCs移植并GS对大鼠脊髓损伤后期修复的影响

目的观察骨髓间充质干细胞（MSCs）移植联合应用促细胞生长物质（GS）对脊髓损伤后期大鼠运动功能修复的影响。方法应用全骨髓法分离培养MSCs,10 mg/L的BrdU标记细胞核。将成年雄性Wistar大鼠36只,以改良Allen打击法制备T10脊髓损伤模型,制模后2周随机分为MSCs＋GS组、MSCs组与对照组,每组12只,伤后2周各组损伤处分别注入MSCs＋GS、单纯MSCs、培养液。分别于伤后1、2、3、4、5、6周进行BBB评分;损伤后6周处死大鼠,取损伤段脊髓及其上下各1 cm组织,行苏木精-伊红染色及SABC免疫组织化学方法染色,观察损伤脊髓组织病理变化和BrdU阳性细胞及GAP-43的相对表达。结果制模后1~2周3组大鼠后肢运动功能BBB评分未见明显差异（F=0.322、0.044,P〉0.05）,3~6周MSCs＋GS组大鼠后肢运动功能BBB评分较MSCs组和对照组高（F=13.729~97.187,P〈0.05）;MSCs＋GS组大鼠脊髓损伤中心及头、尾端均可见BrdU染色阳性细胞。同时,MSCs＋GS组及MSCs组损伤节段脊髓内GAP-43的表达面积明显多于对照组,MSCs＋GS组多于MSCs组。结论 MSCs移植联合GS促进大鼠损伤脊髓结构和功能恢复的效果明显优于单纯细胞移植,两者联用具有协同效应。     

异基因造血干细胞移植后人类疱疹病毒6型感染及其与巨细胞病毒感染的相关性

为了解人类疱疹病毒6型（human herpesvirus 6，HHV-6）在中国接受异基因造血干细胞移植（hematopoietic stem cell transplantation，HSCT）的人群中感染现状及其与巨细胞病毒（cytomegalovirus，CMV）感染的相关性，对72例接受HSCT的患者HHV-6DNA血症进行连续监测。收集HSCT患者移植前和移植后1-12周EDTA抗凝的外周血标本共680份，采用巢式聚合酶链反应检测外周血单个核细胞中HHV-6DNA，并利用Hind Ⅲ限制性内切酶对HHV-6进行基因分型，同时采用免疫荧光法检测CMV抗原血症。结果显示，HSCT后62．5％（45／72）的患者至少1次出现HHV-6DNA血症，首次检出的中位时间为14（7-63）天；除1例患者检出HHV-6A型以外，其余所有HHV-6阳性患者均为HHV-6B型感染。65.3％（47／72）的移植后患者至少1次发生CMV抗原血症，首次检出的中位时间为43（14-105）天。HHV-6与CMV共感染（CMV^＋／HHV-6^＋）的发生率为52．8％（38／72）．HHV-6DNA血症的首次检出时间早于CMV抗原血症（P〈0．0001）。HHV-6DNA血症阳性患者CMV抗原血症检出率显著高于HHV-6血症阴性患者[84．4％（38／45）vs33.3％（9／27），P=0．0001]。HSCT后的疱疹病毒感染相关疾病中出血性膀胱炎（HC）发生率较高[23.6％（17／72）]，其中88．2％（15／17）的HC发生于HHV-6血症阳性患者．82.3％（14／17）发生于CMV^＋／HHV-6^＋患者。结论：HSCT后HHV-6感染以及HHV-6与CMV共感染状态普遍存在，且发生于移植后早期的HHV-6感染与发生时间相对较晚的CMV感染之间可能存在相关性。     

肠内营养支持对危重病人营养状态及内毒素水平影响

目的探讨肠内营养（EN）支持对危重病人营养状态及内毒素水平影响。方法选择64例不能经口进食的危重病人,分为完全肠外营养（TPN）组及TPN＋EN组,TPN组采用完全静脉营养支持,TPN＋EN组在病人营养支持全程或部分时间采用EN营养支持,比较两组病人营养支持前后营养状态、血清内毒素及炎性递质的水平。结果治疗1周后,TPN＋EN组病人血清前血清清蛋白、前清蛋白水平高于TPN组（t=2．92、3．58,P〈0．05）,血清内毒素、白介素6及肿瘤坏死因子a水平低于TPN组（t=3．54～7．36,P〈0．05）。结论EN支持能够改善危重病人的营养状态,减少病人体内细菌内毒素的生成及炎性损伤。