李大金
生殖免疫学研究
个性化签名
- 姓名:李大金
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
妇产科学
- 研究兴趣:生殖免疫学研究
李大金,男,汉族,1957年4月生于江苏扬州;现任复旦大学附属妇产科研究所所长,教授、研究员、博士研究生导师。1992年在上海医科大学获中西医结合妇产科生殖免疫学专业博士学位。主要从事生殖免疫学研究及生殖医学临床医疗及教学工作。2006年入选上海市医学领军人才。先后6次获得国家自然科学基金资助。近年来发表SCI等学术论文140余篇;获卫生部、教育部、上海市及国家中医药管理局等科技进步奖9项。主编学术专著《临床免疫学》、《生殖免疫学》;参编《现代医学免疫学》、《分子免疫学》。荣获1995年度上海市第五届“银蛇奖”三等奖,及1998年度明治乳业生命科学奖。现任中国中西医结合学理事;中国中西医结合学会妇产科专业委员会副主任委员。中华生殖医学会委员;上海市免疫学会理事;中国免疫学会生殖免疫分会委员;上海市计划生育与生殖健康学会理事。《中国中西医结合杂志》编委;《中国中西医结合急救杂志》编委;《中国实用妇科与产科杂志》编委;《国外医学计划生育分册》编委;《国外医学妇幼保健分册》编委。
专家特长:擅长不孕症,习惯性流产,子宫内膜异位症,更年期综合征,卵巢早衰,子宫肌瘤等疾患的中西医结合诊断与治疗;生殖免疫咨询。
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成果数
17
李大金, WANG Yu-dong△, LI Da-Jin, LIANG Fang, and ZHANG Jian-wei
CJM 2003; 9 (2): 93-97,-0001,():
-1年11月30日
Objective: To compare the effects of treatment of tubal pregnancy (TP)and its following second pregnancy by intratubal methotrexate injection (IMI) alone and combination of IMI with Chinese herbal medicine. Metlmds: Thirty-five patients sudferiug from unruptured TP were divided into two groups at random, to the 19 patients in the treated group, the treatment of combined IMI with Ectopic Pregnancy decoction No.2 (EP2, a traditional Chinese medical decoction) was applied, and to the other 16 patients in the control group, IMI alone was applied for control. Sexum concentrations of h-man chorionic gonadotro-pin (HCG), size of the gestational sac, existent time of fetal cardiac beat and peritoneal fluid were measured before and after treatment. And hysterosalpingography were performed 6 months after pnding the treatment to verify the presence of tubal obstruction and the condition of relapse. Results: The treat-ment of all the 35 women was suceessful. The recovery duration of serum β-HCG, disappeerance duration of TP sac and existent time of peritoneal fluid in the treated group were 20.04-7.8 days, 1.24-0.7 months and 10.74-2.9 days respectively, which were significantly different from those in the control group (24.4 4-8.1 days, 3.64-1.7 months and 19.14-3.2 days respectively(P<0.05, P<0.01 and P<0.05 respec-β-tivdy), but the existent time of fetal cardiac beat in the two groups (8.84-1.9 days vs 9.0 4-1.3 days) was not significantly different (P~0.05). The post-treatment oviduct obstructive rate in the two groups was 10.5% and 43.8% respectively, that in the treatment group was less significant (P<0.05). The relapse rate of EP in the treatment group was insignificantly different from that in the control group (5.3% vs 18.8%,P<0.05).usion: The two therapies (IMI alone and IMI combined with EP2) could obtain e-qual efficacy in curing TP. Compared with IMI alone, the combined therapy appears to have the effects of accelerating the resorption of gestational sac and peritoneal fluid, improving the patency of fallopian tube and ameliorating the cirolm~tance of pregnancy, which is hvorable to improvement of the re-pregnancy rate and reduction of the re-occurrence of ectopic pregnancy as well as to the enhancement of the effect of IMI in killing trophocytes. But there is not enough proof to show the potency of EP2 in killing embryo.
methotrexate,, tubal pregnancy,, traditional Chinese medicine
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【期刊论文】分子佐剂C3d上调Raji细胞协同刺激分子B7-1和B7-2的表达(简报)*
李大金, 余敏, 李大金**, 王秀丽, 袁敏敏, 朱影, 姚晓英, 李华萍
分子细胞生物学报,2006,39(1):77-82,-0001,():
-1年11月30日
我们在以往研究中,引人选择性增强体液免疫效应的新型分子佐剂C3d。成功构建了重组避孕疫苗hCGlβ-C3d3,通过免疫Th2型优势的BALB/c小鼠和,Thl型优势的C57BL/6小鼠,显示分子佐剂C3d在不同品系小鼠均使免疫效应从Thl型细胞免疫向Th2型体液免疫偏倚[1-3]。
分子佐剂C3d, hCGβ, B7-1, B7-2
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李大金, 杜美蓉, 闫凤亭, 李大金*, 严缘昌, 李逸平, 金莉萍, 王明雁, 朱影, 袁敏敏, 孟毅
中国药学杂志,2006,41(3):189-192,-0001,():
-1年11月30日
目的:探讨环孢素A(cyclosporin A, CsA)作用于人滋养层细胞差异表达的功能基因。方法:应用抑制性消减杂交筛选110μmol·L-1 CsA作用于JAR细胞系前后差异表达的功能基因,经RT2PCR及蛋白质印迹进一步验证CsA作用前后原代分离的人早孕期滋养层细胞及JAR细胞株titin 表达的变化。结果:CsA作用于人JAR细胞系前后出现6个具有差异表达的基因,其中1 个为已知基因titin,2个为功能未知的mRNA,3个为位于16号染色体上的EST。RT2PCR显示,CsA作用于人滋养层细胞24h后出现titin mRNA的表达,72h达高峰,并呈现明显的剂量依赖性,110μmol·L-1 CsA作用最明显。蛋白质印迹显示,CsA可诱导titin的表达。结论:CsA可能通过诱导滋养层细胞titin的高表达,改变其生物学行为,从而有利于胚胎着床及早期发育。
关键词:环孢素A, 滋养层细胞, 抑制性消减杂交, 反转录2聚合酶链反应, 蛋白质印迹, 肌肉巨球蛋白
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【期刊论文】脱氢表雄酮对鼠成骨细胞及CD4+T细胞协同刺激分子表达的影响
李大金, 王凌, 王玉东, 王文君, 朱影
中华微生物学和免疫学杂民,2006,26(2):110-114,-0001,():
-1年11月30日
目的探讨脱氢表雄酮(DHEA)对成骨细胞(oste0blasts,OB)及CD4+T细胞表达协同刺激分子的调控作用。方法颅骨酶解法培养鼠oB,体外模拟雌激素撤退;免疫磁珠细胞分选(rnag-c cell 9ort,MAC. S)法分离CD4+T细胞;将oB或CD4 T细胞分为对照组、E2及DHEA处理组,并以LPS刺激;以流式细胞术分析OB表面CDS0、CD86以及CD4+T细胞表面CD28、CⅡA4的表达。结果经E2及DHEA处理后,OB表达CDS0、CD86显著增加(P<0.05,P<0.01);CsA可降低对照组及DHEA处理组OB CD80、CD86的表达(P<0.01)。除DHEA组CD28 T细胞百分比增加外(P<0.05),其余各组CD4 T细胞CD28和CIIA4的表达无显著改变(P>0.05)。结论DHEA可上调鼠OB协同刺激分子CDS0、O386表达,该作用可被CsA阻滞;DHEA还上调CD4 T细胞cD28的表达,提示可改善骨。免疫调节网络。
协同刺激分子, DHEA, 成骨细胞, CD4-T细胞
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李大金, Dajin Li*, Xiaoxi Sun, Chaojing Li, Lirong Cai, Yi Meng
Journal of Reproductive Immunology 54(2002)81-92,-0001,():
-1年11月30日
Objectie: to evaluate the effects on fertility by immunization with anti-idiotypic antibodies to porcine zona pellucida (PZP) antigen. Method: anti-idiotypic antibodies (Ab2) were produced in New Zealand rabbits immunized with 17D3 monoclonal antibodies (mAbs) (IgG, Ab1) to PZP antigen. The antisera were first passed through immuno-affinity chromatography column linked to normal mouse IgG so as to remove the antibody bound to normal mouse IgG The passing elute was then purified by immuno-affinity chromatography using 17D3 mAbs to get the Ab2. Female BALB/c mice, 5-week-old, were grouped and immunized with the Ab2, PZP antigen, target antigen of the Ab1 and normal rabbit IgG, respectively. The treated female mice were mated with male BALB/c mice and sacrificed at gestation day 10. Analyses included ELISA measurement of anti-ZP antibody titer, fetal number determination and evaluation of ovarian histomorphology. Results: the Ab2 appeared as a single protein band by SDS-PAGE. Shown by a competitive inhibition ELISA, the Ab2 specifically bound to the variable region of the 17D3 Ab1. Compared with controls, the female mice immunized with Ab2 showed a decreased pregnancy rate and a statistically significant reduction in fetal numbers. Histological examination of ovaries demonstrated that Ab2 exposure interfered less with follicular development than did exposure to PZP. Conclusion: immunization of female mice with Ab2 to PZP mAbs suppresses fertility and fetal numbers with minimal ovarian pathology.
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李大金, Da-Jin Li*, Hong-Mei Wang, Lei Li, Xin-Rong Zhao, Ming-Yan Wang, Ying Zhu, Yi Meng, Min-Min Yuan
Journal of Reproductive Immunology 60(2003)129-141,-0001,():
-1年11月30日
Objective: To express the hCGβ-C3d3 fusion protein in a CHO cell continual expression system to investigate further the adjuvant effects of C3d on contraceptive vaccination. Method: We constructed a plasmid pcDNA3-hCGβ-C3d3 which contains three copies of murine C3d cDNA and the hCGβ gene by cloning the chimerical hCGβ-C3d3 cDNA into the eukaryotic vector pcDNA3 downstream of the CMV promoter. The plasmid was transfected into a COS-7 cell transient expression system and a CHO cell continual expression system. RIA was used to detect hCGβ in the culture supernatant. Western blot and Raji cell immunohistochemical assays were performed to evaluate the expressed protein. Then, 6-/8-week-old female BALB/c mice were inoculated intramuscularly with pcDNA3-hCGβ and pcDNA3-hCGβ-C3d3, and ELISA was used to assess anti-hCGβ IgG antibody in serum. Results: In 72 h after COS-7 cells were transfected with the plasmid pcDNA3-hCGβ-C3d3, 1.0/105 cells could secrete 152 ng of the recombinant protein (calculated by hCGβ contained). The transfected CHO cells, which were then screened by G418, could continuously secrete the fusion protein at 660 ng/106 cells/48 h. The hCGβ-C3d3 protein was purified by anti-hCGβ immunoaffinity chromatography. Raji cell immunohistochemical assay demonstrated that both the hCGβ and C3d3 were successfully fused. After DNA immunization intramuscularly, the anti-hCGβ IgG antibody titer in the pcDNA3-hCGβ-C3d3 immunized group was 243-fold higher than that of the pcDNA3-hCGβ immunized group. Conclusion: We have expressed the hCGβ-C3d3 protein successfully, both in a transient expression system (COS-7 cells) and in a stable expression system (CHO cells). The C3d3 molecular adjuvant can enhance significantly the immunogenecity of hCGβ antigen in DNA immunization.
hCGβ, C3d molecular adjuvant, Expression in vitro, Eukaryotic cell, DNA immunization
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【期刊论文】The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells1
李大金, Xia Wu, Da-Jin Li, Min-Min Yuan, Ying Zhu, and Ming-Yan Wang
BIOLOGY OF REPRODUCTION 70, 1877-1885 (2004),-0001,():
-1年11月30日
Chemokines and chemokine receptors have been implicated as pivotal players in many physiological and pathological situations, but little is known about the expression and function of chemokines and chemokine receptors at the materno-fetal interface. In this study, we first analyzed the transcription of 18 chemokine receptors in first-trimester human trophoblast cells. Among these receptors, CXCR4 was found highly transcribed. We demonstrated afterward that both CXCR4 and CXCL12 (stromal cell-derived factor-1; SDF-1) were expressed in trophoblast cells. Primary cultured trophoblast cells were also found secreting CXCL12 spontaneously. To identify the functional role of CXCR4/CXCL12 in these cells, we treated trophoblast cells with recombinant human (rh) SDF-1a and analyzed the cell viability and signaling pathway. The results showed that rhSDF-1a increased the viability of trophoblast cells and the activation of extracellular signal-regulated kinases signaling pathway in vitro. Our findings suggest that first-trimester trophoblast cells express functional CXCR4/CXCL12, which may play an important role in early pregnancy such as stimulating trophoblast cell proliferation or differentiation in an autocrine manner.
Cytokines, trophoblast
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李大金, Li-Ping Jin, *, Da-Jin Li, Jin-Ping Zhang, †, Ming-Yan Wang, Xiao-Yong Zhu, Ying Zhu, Yi Meng, * and Min-Min Yuan*
The Journal of Immunology, 2004, 173: 3612-3619.,-0001,():
-1年11月30日
The embryo expresses paternal Ags foreign to the mother and therefore has been viewed as an allograft. It has been shown that anergic T cells generated by blocking of the CD28/B7 costimulatory pathway with anti B7-1 and anti B7-2 mAbs can be transferred as suppresser cells to prevent allograft rejection. Little is known, however, about the in vivo function of anti-B7-treated T cells after their transfer into abortion-prone mice in the maintenance of materno-fetal tolerance. In the present study, abortion-prone CBA/J females mated with DBA/2 males were administered anti-B7-1 and anti-B7-2 mAbs on day 4 of gestation (murine implantation window). The anti-B7-treated T cells subsequently were adoptively transferred into abortion-prone CBA/J mice. We demonstrated that costimulation blockade with anti-B7 mAbs at the time of implantation resulted in altered allogeneic T cell response and overcame increased maternal rejection to the fetus in the CBA/J DBA/2 system. The transferred anti-B7-treated T cells appeared to be regulatory, decreasing responsiveness and generating clonal deviation in maternal recipient T cells. The transferred CFSE-labeled T cells were found to reside in the spleen and uterine draining lymph nodes, and a few were localized to the materno-fetal interface of the maternal recipient. Our findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells, but also exert an immunoregulatory effect on the maternal recipient T cells, which cosuppresses maternal rejection to the fetus. This procedure might be considered potentially useful for fetal survival when used as an immunotherapy for human recurrent spontaneous abortion.
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李大金, Xiu-Li Wang, Da-Jin Li*, Min-Min Yuan, Min Yu, Xiao-Ying Yao
Journal of Reproductive Immunology 63(2004)97-110,-0001,():
-1年11月30日
The vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical test demonstrating the feasibility of the approach in preventing pregnancy in women. Some individuals, however, did not response adequately despite employing highly immunogenic bacterial toxoids as carriers. In this study, we investigated the potential of three copies of C3d as a new molecular adjuvant to enhance the immunogenicity of hCGβ protein antigen. The antibody response to the hCGβ-C3d3 fusion protein immunization was compared with those resulting from immunization with the hCGβ alone and the hCGβ plus CFA/IFA either in BALB/c mice or in C57BL/6J mice. Our results showed that the fusion of C3d3 to hCGβ protein antigen resulted in a significant elevation of the serum anti-hCGβ antibody level in the two mouse strains and the antibodies were capable of effectively neutralizing the bioactivity of hCG. The immunization with C3d3 as a molecular adjuvant favored Th2 bias of immune response. The immunity-enhancing effect of the C3d3 was 10-fold (initial) and 20–32-fold (booster) greater than CFA/IFA. These findings indicated that fusion of C3d3 to hCGβ, as a means of harnessing the adjuvant potential of the innate immune system, may improve immunogenicity of the hCGβ contraceptive vaccine, which is useful to produce a cost-effective vaccine and for the less-responsive population.
hCGβ, Protein antigen, C3d3, Molecular adjuvant, Humoral immunity
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李大金, Xiao-Ying Yao, Hong-Mei Wang, Da-Jin Li*, Min-Min Yuan, Xiu-Li Wang, Min Yu, Ming-Yan Wang, Ying Zhu, Yi Meng
Journal of Reproductive Immunology 63(2004)111-122,-0001,():
-1年11月30日
Objectives: To test the possibility of vaccination with lactobacillus expressing hCGβ antigen administered by vaginal mucosal immunization. Methods: A plasmid pIlac-hCGβ was constructed and then transfected into Lactobacillus casei CECT5276, which stably expressed hCGβ protein. RIA was used to detect hCGβ in the culture supernatant and cell lysate.Western blotting was performed to evaluate the expressed protein of interest. Female BALB/c mice aged 6–8 weeks received inoculations in the vagina of the recombinant L. casei CECT5276. ELISA was used to determine the anti-hCGβ IgA antibody in vaginal lavage fluid from the BALB/c mice after vaginal mucosal immunization. Results: The pIlac alone appeared to have a higher efficiency than pIlac-hCGβ, and the highest transfection efficiency of both plasmids was at pulse voltages of 1200V and 1500V. About 78.5% of the hCGβ protein was excreted into the culture supernatant. Excretion of hCGβ was most efficient when the pH of the culture medium was adjusted to around 7.0 and the concentration of lactose was around 1%. The hCG protein in the vaginal lavage fluid of these BALB/c mice was positive on the third day after vaginal inoculation. Anti-hCGβ IgA antibody continued to be found in the vaginal lavage fluid for 2 weeks following a booster vaginal inoculation. The splenic lymphocytes of the mice immunized with hCGβthrough the vagina underwent a proliferative reaction to hCGβ antigen restimulation in vitro. Interferon gamma (IFN-γ) and interleukin (IL)-4 were secreted at higher levels after vaginal mucosal immunization of L. casei expressing hCG than after vaginal mucosal immunization of L. casei alone. Conclusions: Vaginal immunization of lactobacillus expressing hCG induced an antihCGβ antibody response in the murine vaginal mucosa. Induction of the antigen-specific antibodies in the reproductive tract following vaginal inoculation of recombinant lactobacillus will lead to the development of a safe, efficient, and easy-to-use form of immunocontraception.
Recombinant lactobacillus, Immunocontraception, hCGβ, Reproductive tract, Mucosal immunization
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