红斑狼疮间质干细胞（MSCs）异常及脐带MSCs移植治疗狼疮鼠的实验研究
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摘要
目的:
1.探讨系统性红斑狼疮(SLE)患者骨髓间质干细胞(MSCs)的超微结构及细胞骨架的形态学特征及探讨脐带间质干细胞(UC-MSCs)对MRL/lpr狼疮鼠的治疗作用和可能机制。
方法:
体外培养SLE患者的MSCs后,透射电子显微镜(TEM)、激光共聚焦显微镜(LCM)观察超微结构及肌动蛋白、纽蛋白的表达;24只18周龄雌性MRL/lpr小鼠,分为3组:对照组(G1)、UC-MSCs 1次治疗组(G2)、UC-MSCs 3次治疗组(G3)。观察体重,考马斯亮蓝法检测24h尿蛋白含量,酶联免疫吸附法(ELISA)检测抗双链DNA(ds-DNA)抗体水平、血清和尿液单核细胞趋化蛋白-1(MCP-1)水平,观察肾脏、肺、颌下腺病理改变蛋白印迹法检测肾脏MCP-1、高迁移率族蛋白B1(HMGB-1)、基质金属蛋白酶-2(MMP-2)和脾脏Foxp3蛋白水平的表达,实时定量PCR检测肾脏MCP-1、HMGB-1、MMP-2 mRNA和脾脏Poxp3基因表达,免疫组化检测MCP-1以及HMGB-1、MMP-2在肾脏的表达。流式细胞仪检测脾脏、淋巴结中CD4~+CD25~+Foxp3~+T细胞百分率,TUNEL法检测肾脏细胞的凋亡。
结果:
SLE MSCs透射电子显微镜下多数细胞内呈衰老征象,可见大量自噬体;细胞边缘应力纤维增多,排列紊乱,组成粗大的强荧光团,核周围应力纤维减少;纽蛋白在细胞边缘排列紊乱,细胞核周围增多;UC-MSCs移植后显著降低MRL/lpr狼疮鼠24h尿蛋白定量、血肌酐,改善肾脏、肺、颌下腺病理。G1组抗ds-DNA抗体滴度较G3组显著升高。HMGB-1mRNA表达量与血清抗ds-DNA抗体水平(r=0.469,P=0.021)及24h尿蛋白定量(r=0.766,P=0.000)相关。UC-MSCs移植能显著降低MCP-1、HMGB-1、MMP-2在MRL/lpr狼疮鼠肾脏的表达,上调脾脏CD4~+Foxp3~+T淋巴细胞的表达。UC-MSCs移植后系膜区细胞、肾小管间质细胞、肾血管周围浸润的炎性细胞凋亡增加。
结论:
SLE MSCs超微结构及细胞骨架的改变是细胞扩增不良的原因之一;UC-MSCs对MRL/lpr狼疮鼠有显著疗效,安全且无排斥反应;肾小球HMGB-1高表达与MRL/lpr鼠LN相关,抑制MCP-1、HMGB-1、MMP-2的表达及上调调节性T细胞表达,促进肾脏系膜区细胞凋亡,可能与UC-MSCs移植改善LN有关。
Objective
To explore the morphological character of bone marrow-derived mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosus(SLE).To investigate the potential therapeutic effect and the possible mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in the MRL/lpr mice.
Methods
Bone marrow MSCs were isolated from two SLE patients and two healthy controls. Ultrastructural morphology was investigated using transmission electron microscope (TEM). Expression of actin and vinculin were assessed using laser Confocal microscopy (LCM). Twenty four 18-week-old female MRL/lpr mice were divided into 3 groups as following : the group 1(G1) had been treated with 0.5ml Phosphate buffer saline(PBS) as control,the group 2(G2)had been transplanted with 1×10~6 human UC- MSCs through caudal vein, and the group 3 (G3)had been transplanted with 1×10~6 UC- MSCs for three times via the caudal vein. Twenty-four hours proteinuria and bodyweights were assessed every two weeks. The levels of serum anti-ds-DNA antibody, urine and serum monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme linked immunosorbent assay (ELISA) . The histopathology of the kidney, lung and sialaden was observed via immunohistochemical staining. Renal MCP-1, high mobility group box protein-1(HMGB-1), and matrix metalloproteinases-2 (MMP-2) and spleen (Foxp3) gene and protein expression were detecteded by quantitation real time polymerase chain reaction and western blot, respectively. Kidney MCP-1 and HMGB-1, MMP-2 expressions were assessed using immunohistochemistry. The percentage of CD4+ Foxp3+ T cell in spleen and lymph nodes was analyzed by flow cytometry. The kidney cell apoptosis was detected using TUNEL method.
Results
MSCs in patients with SLE have signs of aging: lots of autophagosomes, dense F-actin arranged disorderly at the edge of cytoplasm, dense vinculin arranged disorderly in the cytoplasm. In comparison to mice which received saline alone, mice received three weekly UC-MSCs showed marked reduction of 24h proteinuria, decrease in serum creatinine, and lower anti-ds-DNA antibody level with reduction of renal injury such as crescent formation. Less but significant decreases in these parameters were also observed in mice received single infusion. In comparison to control ground mice, UC-MSCs significantly reduced the extent of interstitial pneumonitis and sialadenitis in the MRL/lpr mice. Expression of HMGB-1 mRNA was positively correlated with the level of serum anti ds-DNA antibodies (r=0.469, P=0.021) and the 24 hours proteinuria (r=0.766, P=0.000). Marked inhibition of expression of MCP-1, HMGB-1 and MMP-2 were observed in the mice treated with UC-MSCs. The G2and G3 MRL/lpr mice had higher percentages of CD4+ Foxp3+ T cells in spleen and lower in lymphoid nodes as compared with controls (P<0.01).The expressions of Foxp3 protein and mRNA of spleen in G2 and G3 were both significantly higher than those in G1 (P<0.05).There was also a significantly difference between G2 and G3(P<0.05). The percentage of apoptotic cells in both the peritubular and perivascular infiltrating cells was also higher in G2 and G3 than in the control group. Besides, in both G2 and G3 mice, the number of apoptotic cells in glomerular mesangium increased significantly, as compared with that in G1 group(P<0.05).
Conclusions
The change of ultrastructure and cytoskeleton may explain why the MSCs from SLE patient showed an abnormal ability of cell expansion in vitro. These findings indicate that UC- MSCs has pleiotropic therapeutic effects on lupus nephritis, pneumonitis, and sialadenitis, suggesting a potential application of UC-MSCs in the treatment of human lupus. High expression of HMGB-1 may contribute to the pathogenesis of lupus nephritis in MRL/lpr mice. By upregulating Treg population and inducing inflammatory cell apoptosis, inhibition of MCP-1, HMGB-1, or MMP-2 may account for some of the therapeutic mechanisms of UC-MSCs in treating MRL/lpr mice.
1.探讨系统性红斑狼疮(SLE)患者骨髓间质干细胞(MSCs)的超微结构及细胞骨架的形态学特征及探讨脐带间质干细胞(UC-MSCs)对MRL/lpr狼疮鼠的治疗作用和可能机制。
方法:
体外培养SLE患者的MSCs后,透射电子显微镜(TEM)、激光共聚焦显微镜(LCM)观察超微结构及肌动蛋白、纽蛋白的表达;24只18周龄雌性MRL/lpr小鼠,分为3组:对照组(G1)、UC-MSCs 1次治疗组(G2)、UC-MSCs 3次治疗组(G3)。观察体重,考马斯亮蓝法检测24h尿蛋白含量,酶联免疫吸附法(ELISA)检测抗双链DNA(ds-DNA)抗体水平、血清和尿液单核细胞趋化蛋白-1(MCP-1)水平,观察肾脏、肺、颌下腺病理改变蛋白印迹法检测肾脏MCP-1、高迁移率族蛋白B1(HMGB-1)、基质金属蛋白酶-2(MMP-2)和脾脏Foxp3蛋白水平的表达,实时定量PCR检测肾脏MCP-1、HMGB-1、MMP-2 mRNA和脾脏Poxp3基因表达,免疫组化检测MCP-1以及HMGB-1、MMP-2在肾脏的表达。流式细胞仪检测脾脏、淋巴结中CD4~+CD25~+Foxp3~+T细胞百分率,TUNEL法检测肾脏细胞的凋亡。
结果:
SLE MSCs透射电子显微镜下多数细胞内呈衰老征象,可见大量自噬体;细胞边缘应力纤维增多,排列紊乱,组成粗大的强荧光团,核周围应力纤维减少;纽蛋白在细胞边缘排列紊乱,细胞核周围增多;UC-MSCs移植后显著降低MRL/lpr狼疮鼠24h尿蛋白定量、血肌酐,改善肾脏、肺、颌下腺病理。G1组抗ds-DNA抗体滴度较G3组显著升高。HMGB-1mRNA表达量与血清抗ds-DNA抗体水平(r=0.469,P=0.021)及24h尿蛋白定量(r=0.766,P=0.000)相关。UC-MSCs移植能显著降低MCP-1、HMGB-1、MMP-2在MRL/lpr狼疮鼠肾脏的表达,上调脾脏CD4~+Foxp3~+T淋巴细胞的表达。UC-MSCs移植后系膜区细胞、肾小管间质细胞、肾血管周围浸润的炎性细胞凋亡增加。
结论:
SLE MSCs超微结构及细胞骨架的改变是细胞扩增不良的原因之一;UC-MSCs对MRL/lpr狼疮鼠有显著疗效,安全且无排斥反应;肾小球HMGB-1高表达与MRL/lpr鼠LN相关,抑制MCP-1、HMGB-1、MMP-2的表达及上调调节性T细胞表达,促进肾脏系膜区细胞凋亡,可能与UC-MSCs移植改善LN有关。
Objective
To explore the morphological character of bone marrow-derived mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosus(SLE).To investigate the potential therapeutic effect and the possible mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in the MRL/lpr mice.
Methods
Bone marrow MSCs were isolated from two SLE patients and two healthy controls. Ultrastructural morphology was investigated using transmission electron microscope (TEM). Expression of actin and vinculin were assessed using laser Confocal microscopy (LCM). Twenty four 18-week-old female MRL/lpr mice were divided into 3 groups as following : the group 1(G1) had been treated with 0.5ml Phosphate buffer saline(PBS) as control,the group 2(G2)had been transplanted with 1×10~6 human UC- MSCs through caudal vein, and the group 3 (G3)had been transplanted with 1×10~6 UC- MSCs for three times via the caudal vein. Twenty-four hours proteinuria and bodyweights were assessed every two weeks. The levels of serum anti-ds-DNA antibody, urine and serum monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme linked immunosorbent assay (ELISA) . The histopathology of the kidney, lung and sialaden was observed via immunohistochemical staining. Renal MCP-1, high mobility group box protein-1(HMGB-1), and matrix metalloproteinases-2 (MMP-2) and spleen (Foxp3) gene and protein expression were detecteded by quantitation real time polymerase chain reaction and western blot, respectively. Kidney MCP-1 and HMGB-1, MMP-2 expressions were assessed using immunohistochemistry. The percentage of CD4+ Foxp3+ T cell in spleen and lymph nodes was analyzed by flow cytometry. The kidney cell apoptosis was detected using TUNEL method.
Results
MSCs in patients with SLE have signs of aging: lots of autophagosomes, dense F-actin arranged disorderly at the edge of cytoplasm, dense vinculin arranged disorderly in the cytoplasm. In comparison to mice which received saline alone, mice received three weekly UC-MSCs showed marked reduction of 24h proteinuria, decrease in serum creatinine, and lower anti-ds-DNA antibody level with reduction of renal injury such as crescent formation. Less but significant decreases in these parameters were also observed in mice received single infusion. In comparison to control ground mice, UC-MSCs significantly reduced the extent of interstitial pneumonitis and sialadenitis in the MRL/lpr mice. Expression of HMGB-1 mRNA was positively correlated with the level of serum anti ds-DNA antibodies (r=0.469, P=0.021) and the 24 hours proteinuria (r=0.766, P=0.000). Marked inhibition of expression of MCP-1, HMGB-1 and MMP-2 were observed in the mice treated with UC-MSCs. The G2and G3 MRL/lpr mice had higher percentages of CD4+ Foxp3+ T cells in spleen and lower in lymphoid nodes as compared with controls (P<0.01).The expressions of Foxp3 protein and mRNA of spleen in G2 and G3 were both significantly higher than those in G1 (P<0.05).There was also a significantly difference between G2 and G3(P<0.05). The percentage of apoptotic cells in both the peritubular and perivascular infiltrating cells was also higher in G2 and G3 than in the control group. Besides, in both G2 and G3 mice, the number of apoptotic cells in glomerular mesangium increased significantly, as compared with that in G1 group(P<0.05).
Conclusions
The change of ultrastructure and cytoskeleton may explain why the MSCs from SLE patient showed an abnormal ability of cell expansion in vitro. These findings indicate that UC- MSCs has pleiotropic therapeutic effects on lupus nephritis, pneumonitis, and sialadenitis, suggesting a potential application of UC-MSCs in the treatment of human lupus. High expression of HMGB-1 may contribute to the pathogenesis of lupus nephritis in MRL/lpr mice. By upregulating Treg population and inducing inflammatory cell apoptosis, inhibition of MCP-1, HMGB-1, or MMP-2 may account for some of the therapeutic mechanisms of UC-MSCs in treating MRL/lpr mice.
引文
1.Rockall AG,Rickards D,Shaw PJ.Imaging of the pulmonary manifestations of systemic disease.Postgrad Med J,2001,77:621-638.
2.Majumdar MK,Thiede MA,Haynesworth SE.Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stroml and osteogenic lineages.J Hematother Stem Cell Res,2000,9:841-848.
3.Frank MH,Sayegh MH.Immunomodulatory functions of mesenchymal stem cells.Lancet,2004,363:1411-1412.
4.Aggarwal S,Pittenger MF.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
5.Fontenot JD,Gavin MA,Rudensky AY.Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.Nat Immunol,2003,4:330-336.
6.赵盛楠,孙凌云.糖皮质激素对系统性红斑狼疮CD4+Foxp3+T细胞水平的影响.中华风湿病学杂志,2008,12:166-169.
7.Zhang J,Roschke V,Baker KP,et al.Cutting edge:a role for B lymphocyte stimulator in systemic lupus erythematosus.J Immunol,2001,166:6-10.
8.Schiemann B,Gommerman JL,Vora K,et al.An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway.Science,2001,293:2111-2114.
9.Giuseppe G,Loreto G,ElenaRanieri,et al.Monocyte chemoattractant peptide-1 expression in acute and chronic human nephritides apathogenetic role in interstitial monocyte srecruitment.J Am Soc Nephrol,1996,7:906-911.
10.Wada T,Yokoyama H,Su SB,et al.Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.Kidney Int,1996,49:761-767.
11.Noris M,Bernasconi S,Casiraghi F,et al.Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.Lab Invest,1995,73:804-809.
12.Lima G,Soto-Vega E,Atisha-Fregoso Y,et al.MCP-1,RANTES,and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus.Hum Immunol,2007,68:980-985.
13.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein-1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
14.蔡广研,陈香美,王兆霞,等.MRL/lpr狼疮小鼠肾脏明胶酶表达随增龄变化及意义.中华病理学杂志,2002,31:432-435.
15.Tveita AA,Rekvig OP,Zykova SN.Increased glomerular matrix metalloproteinase activity in murine lupus nephritis.Kidney Int,2008,74:1150-1158.
16.Ikehara S.Autoimmune diseases as stem cell disorders:normal stem cell transplant for their treatment.Int J Mol Med,1998,1:5-16.
17.Ikehara S.Bone marrow transplantation for autoimmune disease.Acta Haematol,1998,99:116-132.
18.孙凌云.自身免疫病-造血干细胞病.中华风湿病杂志,2000,4:5-6.
19.Ikehara S.New strategies for allogeneic BMT.Bone Marrow Transplant,2003,32:S73-75.
20.Papadaki HA,Boumpas DT,Gibson FM,et al.Increased apoptosis of bone marrow CD34+ cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus.Br J Haematol,2001,115:167-174.
21.徐婷,金鸥阳,赵盛楠,等.系统性红斑狼疮患者骨髓间充质干细胞多向分化能力异常.中华风湿病杂志,2009,13:185-186.
22.Zhou K,Zhang H,Jin O,et al.Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.Cell Mol Immunol.2008,5:417-24.
23.Rao M S,Mattson M P.Stem cells and aging:expanding the possibilities.Mech Ageing Dev,2001,122:713-734.
24.金鸥阳,张华勇,徐婷,等.青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制.实用临床医药杂志,2007,11:5-9.
1.孙凌云.自身免疫病-造血干细胞病.中华风湿病学杂志,2000,4:5-6.
2.张华勇,冯学兵,孙凌云.系统性红斑狼疮患者骨髓间质干细胞生物学特性及对造血支持的研究.中华风湿病学杂志,2006,6:331-334.
3.Kalia N,Pockley AG,Wood RF,et al.Effects of FK409 on intestinal ischemia-reperfusion injury and ischemia-induced changes in the rat mucosal villus microcirculation.Transplantation,2001,72:1875-1880.
4.Bras M,Queenan B,Susin SA.Programmed cell death via mitochondria:different modes of dying.Biochemistry,2005,70:231-239.
5.Qin ZH,GU ZL.Huntingtin processing in pathogenesis of Huntington disease.Acta Pharmacol Sin,2004,25:1243-1249.
6.Fridman R,Scott AF,Muller D,et al.The role of cell adhesion and migration in the in vitro invasiveness of mouse adkidney carcinoma cells.Invasion Metastasis,1990,10:208-214.
7.Kuroda N,Naruse K,Miyazaki E,et al.Vinculin:its possible use as a marker of normal collecting ducts and kidney neoplasms with collecting duct system phenotype.Mod Pathol,2000,13:1109-1114.
8.Kogan O,Yarden A,Gimona M,et al.Preliminary crystallographic study of turkey gizzard vinculin.Acta Crystallogr D Biol Crystallogr,2000,56:1055-1057.
9.Coll JL,Ben-Ze'ev A,Ezzell RM,et al.Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell morphology,adhesion,and locomotion.Proc Natl Acad Sci,1995,92:6161-6165.
10.Kawahara E,Tokuda R,Nakanishi I.Migratory phenotypes of Hsc-3 squamous carcinoma cell line induced by EGF and PMA:relevance to migration of loosening of adhesion an vinculin-associated focal contacts with prominent filopodia.Cell Biol Int,1999,23:163-174.
11.Perez M M,Jamora C,Fuchs E.Stickly business:orchestrating cellular singnals at adherens junctions.Cell,2003,112:535-548.
12.Geiger B,Volk T,Volberg T,et al.Molecular interactions in adherens-type contacts.J Cell Sci,1987,8:251-272.
13.荣明,石玉秀.纽蛋白在原代培养神经元的分布及其与神经元形态的相关性.中国组织化学与细胞化学杂志,2002,11:4-7.
14.Watanabe N,Ando K,Yoshida S,et al.Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium.Biochem Biophys Res commun,2002,294:1121-1129.
1.Andonopouls A P,Constantopoulos SH,Galanopoulou V,et al.Pulmonary of non-smokimg patients with systemic lupus.Chest,1988,94:312-315.
2.Ikehara S.New strategies for allogeneic BMT.Bone Marrow Transplantation.2003,32:S73-75.
3.Duffield JS,Bonventre JV.Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury.Kidney Int,2005,68:1956-1961.
4.Sun L Y,Zhang H Y,Feng X B,et al.Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus.Lupus,2007,16:121-128.
5.顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓间质干细胞超微结构及细胞骨架的特征.中华风湿病病学杂志,2008,12:397-400.
6.Rao M S,Mattson M P.Stem cells and aging:expanding the possibilities.Mech Ageing Dev,2001,122:713-734.
7.Atsushi Sadanaga,Hitoshi Nakashima,Kohsuke Masutani,et al.Amelioration of autoimmune nephritis by Imatinib in MRL/lpr mice.Arthritis Rheum,2005,12:3987-3996.
8.Hasegawa H,Inoue A,Muraoka M,et al.Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice.Arthritis Research Therapy,2007,9:R15-27.
9.Aggarwal S,Pittenger M F.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
10.Le Blanc K,Rasmusson I,Sundberg B,et al.Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.Lancet,2004,363:1439-1441.
11.Tse WT,Pendleton JD,Beyer WM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
12.Le BlancK,Tammik L,Rosendahl K,et al.HLA expression and immunologic properties of undifferentiated and differentiated mesenchymal stem cells.Exp Hematol,2003,31:890-896.
13.Shi M,Li J,Liao L,et al.Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment:role in homing efficiency in NOD/SCID mice.Haematologica,2007,92:897-904.
14.田兆方,杜江,王斌,等.人骨髓源性MSCs移植新生大鼠的实验研究.广东医学,2006,27:1461-1463.
15.颜小华,陈晓.脐血间充质干细胞静脉移植治疗新生大鼠缺血缺氧性脑损伤.中国新生儿科杂忐,2006,21:158-161.
16.Zhou K,Zhang H,Jin O,et al.Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.Cell Mol Immunol,2008,5:417-24.
17.孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11:2-5.
18.Plumas J,Chaperot L,Richard MJ,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19:1597-1604.
19.Togel F,Hu Z,Weiss K,et al.Administered mesenchymal stem cells protect against ischemic acute kidney failure through differentiation-independent mechanisms.Am J Physiol Kidney Physiol,2005,289:F31-F42.
20.Ninichuk V,Gross O,Segerer S,et al.Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice.Kidney Int,2006,70:121-129.
21.Rojas M,Xu J,Woods CR,et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol,2005,33:145-152.
22.Ortiz LA,Gambelli F,McBride C,et al.Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.PNAS,2003,100:8407-8411.
23.赵峰,李圣青,张宇飞,等.骨髓间充质干细胞在肺损伤大鼠肺组织的分化.解放军医学杂志,2007,32:131-133.
1.Giuseppe G,Loreto G,Ranieri E,et al.Monocyte chemoattractant peptide-1 expression in acute and chronic human nephritides apathogenetic role in interstitial monocytes recruitment.J Am Soc Nephrol,1996,7:906-913.
2.Wada T,Yokoyama H,Su SB,et al.Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.Kidney Int,1996,49:761-767.
3.Noris M,Bernasconi S,Casiraghi F,et al.Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.Lab Invest,1995,73:804-809.
4.Lima G,Soto-Vega E,Atisha-Fregoso Y,et al.MCP-1,RANTES,and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus.Hum Immunol,2007,68:980-985.
5.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein-1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
6.Bianchi ME,Beltrame M.Upwardly mobile proteins.Workshop:the role of HMG proteins in chromatin structure,gene expression and neoplasia.Embo Rep,2000,1:109-114.
7.Taniguchi N,Kawahara K,Yone K,et al.High mobility group box chromosomal protein 1 plays a role in pathogenesis of rheumatoid arthritis as a novel cytokine.Arthritis Rheum,2003,48:971-981.
8.Kokkola R,Sundberg E,Ulfgren AK,et al.High mobility group box chromosomal protein 1:a novel proinflammatory mediator in synovitis.Arthritis Rheum,2002,46:2598-2603.
9.Pullerits R,Jonsson IM,Verdrengh M,et al.High mobility group box chromosomal protein 1,a DNA binding cytokine,induces arthritis.Arthritis Rheum,2003,48:1693-1700.
10.Kokkola R,Li J,Sunberg E,et al.Successful treatment of collagen-induced arthritis in mice and rats by target in extracellular high mobility group box chromosomal protein 1 activity.Arthritis Rheum,2003,48:2052-2058.
11.Popovic K,EK M,Espinosa A,et al.Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus.Arthritis Rheum,2005,52:3639-3645.
12.周健光,蔡绥,郑敏.高迁移率族蛋白-1在狼疮性肾炎中的表达.中华医学会第十二次全国 皮肤性病学术会议论文集,2006:86.
13.陈荣权,陈香美,崔世维,等.明胶酶及其抑制物在衰老大鼠肾组织中的表达及意义.中国老年学杂志,2004,24:129-132.
14.蔡广研,陈香美,王兆霞,等.MRL/lpr狼疮小鼠肾脏明胶酶表达随增龄变化及意义.中华病理学杂志,2002,31:432-435.
15.Tveita AA,Rekvig OP,Zykova SN.Increased glomerular matrix metalloproteinase activity in murine lupus nephritis.Kidney Int,2008,74:1150-1158.
16.Fontenot JD,Gavin MA,Rudensky AY.Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells.Nat Immunol,2003,4:330-336.
17.赵盛楠,孙凌云.糖皮质激素对系统性红斑狼疮CD4~+Foxp3~+T细胞水平的影响.中华风湿病学杂志,2008,12:166-169.
18.Colotta F,Sciacca FL,Sironi M,et al.Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin.Am J Pathol,1994,144:975-985.
19.Maus U,Henning S,Wenschuh H,et al.Role of endothelial MCP-lin monocyte adhesion to inflamed human endothelium under physiological flow.Am J Physiol Heart Circ Physiol,2002,283:H2584-H2591.
20.Maslin CL,Kedzierska K,Webster NL,.et al.Transendothelial migration of monocytes:the underlying molecular mechanisms and consequences of HIV-1 infection.Curr HIV Res,2005,3:303-317.
21.Zoja C,Liu XU,Donadelli R,et al.Kidney expression of monocyte chemoattractant protein-1in lupus autoimmune mice.J Am Soc Nephrol.1997,8:720-729.
22.Adams DH,Shaws S.Leucocyte-endothelial interactions and regulation of leucocyte migration.Lancet,1994,343:831-836.
23.Wada T,Furuichi K,Segawa-Takaeda C,et al.MIP-lalpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.Kidney Int,1999,56:995-1003.
24.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
25.Zoja C,Corna D,Benedetti G,et al.Bindarit retards kidney disease and prolongs survival in murine lupus autoimmune disease.Kidney Int,1998,53:726-734.
26.Hitoshi H,Masashi K,Miho S,et al.Antagonist of monocyte chemoattractant protein 1ameliorates the initiation and progression of lupus nephritis and kidney vasculitis in MRL/lpr mice.Arthritis & Rheum,2003,48:2255-2266.
27.Tse KC,Lam MF,Tang SC,et al.A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade.Lupus,2007,16:46-51.
28.Mok CC,Tong KH,To CH,et al.Tacrolimus for induction therapy of diffuse proliferative lupus nephritis:an open-labeled pilot study.Kidney Int,2005,68:813-817.
29.Lenz O,Contreras G.Treatment options for severe lupus nephritis.Arch Immunol Ther Exp,2004,52:356-365.
30.Politt D,Heintz B,Floege J,et al.Tacrolimus(FK506) based immunosuppression in severe systemic lupus erythematosus.Clin Nephrol,2004,62:49-53.
31.Maruyama M,Yamasaki Y,Sada K,et al.Good response of membranous lupus nephritis to tacrolimus.Clin Nephrol,2006,65:276-279.
32.Tam LS,Li EK,Wong CK,et al.Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy:an open label trial.Ann Rheum Dis,2006,65:417-418.
33.Degryse B,De Virgilio M.The nuclear protein HMGB-1,a new kind of chemokine? FEBS Lett,2003,553:11-17.
34.Yamamoto Y,Kato I,Doi T,et al.Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice.J Clin Invest,2001,108:261-268.
35.Pawar RD,Patole PS,Ellwart A,et al.Ligands to nucleic acid-specific toll-like receptors and the onset of lupus nephritis.J Am Soc Nephrol,2006,17:3365-2273.
36.Uesugi H,Ozaki S,Sobajima J,et al.Prevalence and characterization of novel pANCA,antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2,in systemic rheumatic diseases.J Rheumatol,1998,25:703-709.
37.Deocharan B,Zhou JJ,Antar K,et al.Alpha-actinin immunization elicits anti-chromatin autoimmunity in nonautoimmune mice.J Immunology,2007,179:1313-1321.
38.Stemmann-Niggh K,Ziswiler R,Kung M,et al.Inhibition of matrix metalloproteinases attenuates anti-Thy1 nephritis.J Am Soc Nephrol,1998,9:397-407.
39.McMillan JI,Riordan JW,Couser WG,et al.Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteninase-9 with enhanced expression in a model of membranous nephropathy.J Clin Invest,1996,97:1094-1101.
40.Nakamura T,Ebihara I,Tomino,et al.Effect of a specific endothelin A receptor antagonist on murine nephritis.Kidney Int,1995:51:481-489.
41.Lu LL,Liu YJ,Yang SG,et al.Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials.Haematologica,2006,91:1017-1026.
42.Shinizu A,Kitamura H,Masuda Y,et al.Apoptosis in the repair process of experimental proliferative glomerulonephritis.Kidney Int,1995,47:114-121.
43.Soto H,Mosquera J,Hemriquez La Roche C,et al.Apoptosis in proliferative glomerulonephritis:decreased apoptosis expression in lupus nephritis.Nephrol Dial Transplant,1997,12:273-280.
44.Lu F,Shen W,Zhang X,et al.Dysregulation of apoptosis:a possible mechanism leading to chronic progressive kidney histological changes in lupus nephritis.Chin Med J(Engl),2000,113:1082-1086.
45.王建中,廖洪军,陈香美,等.甲基泼尼松龙对狼疮小鼠肾脏细胞凋亡及ICE基因表达的影 响.中华内科学,1997,36:79-82.
46.孙秀珍,谢蜀生,龙振洲,等.青蒿素及其衍生物免疫抑制作用的实验研究.中西医结合杂志,1991,11:37-38.
47.仰锦虹,李道中.抗疟药蒿甲醚注射液对小鼠免疫功能的影响.广州中医学院学报,1990,7:102-105.
48.陈华,高玉祥.青蒿琥酯免疫作用机制的探讨.中华皮肤科杂志,1990,23:250-252.
49.郭兴伯,符林春,范太涛,等.青蒿琥酯静脉注射治疗脑型疟疾33例临床报告.广州中医学院学报,1993,9:1-3.
50.郭兴伯,符林春,简华香,等.健康人静脉注射青蒿琥酯的酎受性和毒副反应研究.中药新药与临床药理,1991,2:29.
51.钟嘉熙,刘亚敏,刘红姣,等.青蒿琥酯治疗系统性红斑狼疮的安全性观察.中药新药与临床药理,2000,11:336.
52.朱卫星,顾军.青蒿琥酯对狼疮样小鼠血清白细胞介素-6和转化生长因子-β的影响.中国麻风皮肤病杂志,2004,20:318-319.
53.徐丽敏,陈学荣.双氢青蒿素对狼疮性BXSB小鼠的作用.中国中西医结合皮肤性病学杂志,2002,1:19-20.
54.张剑勇,钟嘉熙.苓丹片,青蒿琥酯对SLE小鼠T淋巴细胞亚群的影响.中药药理与临床,1998,14:27-29.
55.张剑勇,钟嘉熙,彭胜权,等.苓丹片,青蒿琥酯对系统性红斑狼疮患者IL-2与sIL-2R 影响的研究.河南中医学院学报,2003,18:38-39.
56.董妍君,李卫东,屠呦呦,等.双氢青蒿素对BXSB狼疮小鼠自身抗体产生,TNFa分泌及狼疮性肾炎病理改变的影响.中国中西医结合杂志,2003,23:676-679.
57.董妍君,李卫东,屠呦呦,等.双氢青蒿素对BXSB小鼠狼疮肾炎的作用及机制研究.中国药理学通报,2003,19:1125-1128.
58.金鸥阳,张华勇,徐婷,等.青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制.实用临床医药杂志,2007,11:5-9.
1.Friendenstein AJ,Chailakhyan RK,Gerasimov UV.Bone marrow osteogenic stem cells:in vitro cultivation and transplantation in diffusion chambers.Cell Tissue Kinet,1987,20:263-272.
2.Majumdar MK,Keane-Moore M,Buyaner D,et al.Characterization and functionality of cell surface molecules on human mesenchymal stem cells.J Biomed Sci,2003,10:228-241.
3.Bogenrieder T,Herlyn M.Axis of evil:molecular mechanisms of cancer metastasis.Oncogene,2003,22:6524-6536.
4.Li Y,Hisha H,Inaba M,et al.Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection. Exp Hematol, 2000, 28: 950-960.
5. Krampera M, Cosmi L, Angeli R, et al. Role of IFN-g in the immunomodulatory activity of human mesenchymal stem cells. Stem Cells, 2005, 24: 386-98.
6. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol, 2002, 30: 42-48.
7. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 2003,102: 3837-3844.
8. Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol, 2003,31: 890-896.
9. Farrington-Rock C, Crofts NJ, Doherty MJ, et al. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation, 2004,110: 2226-32.
10. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone MinerRes. 2003, 18: 696-704.
11. Da Silva Meirelles L, Chagastelles PC. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci, 2006,119: 2204-2213.
12. Wexler SA, Donaldson C, Denning-Kendall P, et al. Adult bone marrow is a rich source of human mesenchymal stem cells but umbilical cord and mobilized adult blood are not. Br J Haematol, 2003, 121:368-374.
13. Kassem M, Kristiansen M, Abdallah BM. Mesenchymal stem cells:Cell biology and potential use in therapy. Pharmacol Toxicol, 2004, 95: 209-214.
14. Von Luttichau I, Notohamiprodjo M, Wechselberger A, et al. Human adult CD34-progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4. Stem Cells Dev, 2005,14: 329-336.
15. Lopez PA, Marais EA, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: Comparison of chemokine and growth factor chemotactic activities. Stem Cells, 2007, 25:1737-1745.
16. Schmidt A, Ladage D, Schinkothe T, et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells , 2006, 24: 1750-1758.
17. Fiedler J, Brill C, Blum WF, et al. IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Biochem Biophys Res Commun, 2006, 345: 1177-1183.
18. Neth P, Ciccarella M, Egea V, et al. Wnt signaling regulates the invasion capacity of human mesenchymal stem cells. Stem Cells, 2006, 24: 1892-1903.
19. Oliver JA, Maarouf O, Cheema FH, et al. The kidney papilla is a niche for adult kidney stem cells. J Clin Invest, 2004, 114: 795-804.
20. Plumas J, Chaperot L, Richard MJ, et al. Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia, 2005, 19: 1597-1604.
21. Ito T, Suzuki A, Imai E, et al. Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling. J Am SocNephrol, 2001,12: 2625-2635.
22. Duffield JS, Bonventre JV. Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int, 2005, 68: 1956-1961.
23. Morigi M, Imberti B, Zoja C, et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute kidney failure. J Am Soc Nephrol, 2004,15:1794-1804.
24. Lange C, Togel F, Ittrich H, et al. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute kidney failure in rats. Kidney Int, 2005, 68:1613-1617.
25. Kunter U, Rong S, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol, 2006,17: 2202-2212.
26. Ninichuk V, Gross O, Segerer S, et al. Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int, 2006, 70:121-129.
27. Zhou K, Zhang H, Jin O, et al. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol, 2008, 5: 417-424.
1.PittingerM,Mackay A,Beck S,et al.Multilineage potential of adult human mesenchymal stem cells.Science,1999,284:143-147.
2.Chen LB,Jiang XB,Yang L.Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells.Word J Gastroenterol,2004,10:3016-3020.
3.Chao KC,Chao KF,Fu YS,et al.Islet-like clusters derived from mesenchymal stem cells in wharton's jelly of the human umbilical cord for transplantation to control type 1 diabetes.PLoS ONE,2008,3:e1451.
4.Le Blanc K,Tammik L,Zetterberg E,et al.HLA-expression and immunologic properties of undifferentiated and differentiated mesenchymal stem cells.Exp Hematol,2003,31:890-896.
5.TseWT,Pendleton JD,BeyerWM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
6.Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by differentme chanisms.Exp Cell Res,2005,305:33-41.
7.Bartholomew A,Sturgeon C,SiatskasM,et at.Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.Exp Hemato,2002,30:42-48.
8.Jiang XX,Zhang Y,Liu B,et al.Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.Blood,2005,105:4120-4126.
9.Aggarwal S,Pittenger MF.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
10.Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit the formation of cytotoxic lymphocytes(CTL),but not activated CTL or natural killer(NK) cells.Transplantation,2003,76:1208-1213.
11.Le Blanc K,Rasmusson I,Gotherstrom C,et al.Mesenchymal stem cells inhibit the expression of CD25(interleukin-2 receptor) and CD38 on phytohae magglutinin-activated lymphocytes.Scand J Immunol,2004,60:307-315.
12.Krampera M,Glennie S,Dyson J,et al.Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.Blood,2003,101:3722-3729.
13.Holz A,Brett K,Oldstone MB.Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes.J Clin Invest,2001,108:1749-58.
14.Szelachowska M,Kretowski A,Kinalska I.Increased in vitro interleukin-12 production by peripheral blood in high-risk IDDM first degree relatives.Horm Metab Res,1997,29:168-171.
15.Ozer G,Teker Z,Cetiner S,et al.Serum IL-1,IL-2,TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings.J Pediatr Endocrinol Metab,2003,16:203-210.
16.Campbell IL,Iscaro A,Harrison LC.IFN-gamma and tumor necrosis factor-alpha,Cytotoxicity to murine islets of Langerhans.J Immunol,1988,141:2325-2329.
17.Yoon JW,Jun HS,Santamaria P.Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells.Autoimmunity,1998,27:109-122.
18.Overbergh L,Decallonne B,Branisteanu DD,et al.Acute shock induced by antigen vaccination in NOD mice.Diabetes,2003,52:335-341.
19.H(u|¨)bner MP,Thomas Stocker J,Mitre E.Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3(+) regulatory T cells.Immunology.2008.[Epub ahead of print].
20.Kodama S,K(u|¨)htreiber W,Fujimura S,et al.Islet regeneration during the reversal of autoimmune diabetes in NOD mice.Science,2003,302:1223-1227.
21.李立人,徐青.骨髓基质干细胞移植对糖尿病大鼠血糖的影响.苏州大学学报,2005,25:584-585.
22.Wu T,Levay-Young B,Heuss N,et al.Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy.Transplantation,2002,74:22-27.
23.Ikebukuro K,Adachi Y,Yamada Y,et al.Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats.Transplantation,2002,73:512-518.
24.Lee RH,Seo MJ,Reger RL,et al.Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and kidney glomeruli in diabetic NOD/scid mice.Proc Natl Acad Sci U S A,2006,103:17438-17443.
25.顾志峰,金鸥阳,徐婷,等.脐带间质干细胞移植治疗MRL/lpr狼疮鼠的疗效.中华风湿病学杂志,2009,13:4-7.
26.顾志峰,金鸥阳,徐婷,等.脐带间质干细胞移植对MRL/lpr狼疮鼠间质性肺炎的影响.中华结核和呼吸杂志,2009,32:33-37.
1.王海颖.陈以平教授治疗狼疮性肾炎的经验.新中医,2001,33:9-10.
2.盛梅笑,王身菊.狼疮性肾炎中医临床证候分型的调研分析.江苏中医药,2004,25:12-14.
3.王维英.姚树锦治疗狼疮性肾炎经验介绍.陕西中医,2000,21:463-464.
4.姜兆荣,莫成荣.″毒损肾络″理论在狼疮性肾炎中的应用.中医药学刊,2004,22:1735-1735.
5.王欢,李继科,漆剑.艾儒棣教授治疗气阴两虚证狼疮性肾炎经验.四川中医,2007,25:2-3.
6.于伟,郑慧文.狼疮性肾炎中医病机与治法.浙江中医学院学报,1999,23:18-19.
7.王付民.活血化瘀治疗狼疮性肾炎.辽宁中医杂志,1994,21:454-455.
8.茅建春,苏励,顾军花,等.陈湘君治疗狼疮性肾炎的经验.辽宁中医杂志,2004,31:182-183.
9.刘玉宁,邓跃毅,王立红.陈以平教授治疗狼疮性肾炎的经验.中国中西医结合肾病杂志,2003,4:437-438.
10.曹惠芬,林丽.孟如教授治疗系统性红斑狼疮的经验.云南中医中药杂志,1999,20:1-3.
11.廖晨晖.狼疮性肾炎的中医治疗临床体会.中华实用中西医杂志,2000,1:2637-2638.
12.张世涛.何学红诊治狼疮性肾炎经验.实用中医药杂志,2007,23:377.
13.高景环,孟祥震.狼疮性肾炎临床诊治体会.天津中医药,2007,24:201-202.
14.史伟,唐爱华.中西医结合分阶段治疗狼疮性肾炎32例.现代中西医结合杂志,2000,9:1858-1860.
15.朱辟疆.狼疮性肾炎分型分阶段中西医结合治疗.中国中西医结合肾病杂志,2003,4:358-361.
16.米杰,孙素平.周翠英中西医结合治疗狼疮性肾炎经验.山东中医药大学学报,2006,30:316-317.
17.盛梅笑,王钢.狼疮性肾炎中医病机与治法探讨.中国中医基础医学杂志,2003,9:55-57.
18.李宝丽,庄鸿贤.狼疮性肾炎的病因病机及分期论治.山东中医杂志,2002,21:199-201.
19.阳晓,叶任高.38年中西医结合治疗肾脏病的临床和实验研究.中山医科大学学报,2000,21:401-408.
20.李春雯,金友,牛家臣.中西医结合治疗狼疮性肾炎临床观察.黑龙江中医药,2003,4:22.
21.杨林,成慧贞.中西医结合治疗狼疮性肾炎36例临床研究.河北中医,2003,25:698-700.
22.陈湘君,顾军花.复方自身清治疗活动性SLE的临床观察.上海中医药杂志,1999,16:18.
23.王萍,张广中,王禾,等.养阴益气解毒法治疗系统性红斑狼疮探讨.中国中西医结合皮肤性病学杂志,2003,2:79-82.
24.祁爱蓉,易铁钢,刘学耀,等.滋肾解毒活血中药对狼疮性肾炎系膜增殖的影响.广州中医 药大学学报,2007:24:104-108.
25.李相友,方敬爱.中西医结合治疗重症狼疮肾炎128例.中国医刊,2000,35:46-47.
26.母小真,陈湘君.补肾固精方治疗BXSB小鼠狼疮性肾炎的实验研究.上海中医药大学学报,2007,21:53-55.
27.李玉堂,刘学耀.中西医结合治疗难治性狼疮性肾炎18例.湖北中医杂志,2001,23:19.
28.眭书魁,李立.狼疮饮治疗系统性红斑狼疮的临床研究.河北中医,2000,22:85-89.
2.Majumdar MK,Thiede MA,Haynesworth SE.Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stroml and osteogenic lineages.J Hematother Stem Cell Res,2000,9:841-848.
3.Frank MH,Sayegh MH.Immunomodulatory functions of mesenchymal stem cells.Lancet,2004,363:1411-1412.
4.Aggarwal S,Pittenger MF.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
5.Fontenot JD,Gavin MA,Rudensky AY.Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.Nat Immunol,2003,4:330-336.
6.赵盛楠,孙凌云.糖皮质激素对系统性红斑狼疮CD4+Foxp3+T细胞水平的影响.中华风湿病学杂志,2008,12:166-169.
7.Zhang J,Roschke V,Baker KP,et al.Cutting edge:a role for B lymphocyte stimulator in systemic lupus erythematosus.J Immunol,2001,166:6-10.
8.Schiemann B,Gommerman JL,Vora K,et al.An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway.Science,2001,293:2111-2114.
9.Giuseppe G,Loreto G,ElenaRanieri,et al.Monocyte chemoattractant peptide-1 expression in acute and chronic human nephritides apathogenetic role in interstitial monocyte srecruitment.J Am Soc Nephrol,1996,7:906-911.
10.Wada T,Yokoyama H,Su SB,et al.Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.Kidney Int,1996,49:761-767.
11.Noris M,Bernasconi S,Casiraghi F,et al.Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.Lab Invest,1995,73:804-809.
12.Lima G,Soto-Vega E,Atisha-Fregoso Y,et al.MCP-1,RANTES,and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus.Hum Immunol,2007,68:980-985.
13.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein-1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
14.蔡广研,陈香美,王兆霞,等.MRL/lpr狼疮小鼠肾脏明胶酶表达随增龄变化及意义.中华病理学杂志,2002,31:432-435.
15.Tveita AA,Rekvig OP,Zykova SN.Increased glomerular matrix metalloproteinase activity in murine lupus nephritis.Kidney Int,2008,74:1150-1158.
16.Ikehara S.Autoimmune diseases as stem cell disorders:normal stem cell transplant for their treatment.Int J Mol Med,1998,1:5-16.
17.Ikehara S.Bone marrow transplantation for autoimmune disease.Acta Haematol,1998,99:116-132.
18.孙凌云.自身免疫病-造血干细胞病.中华风湿病杂志,2000,4:5-6.
19.Ikehara S.New strategies for allogeneic BMT.Bone Marrow Transplant,2003,32:S73-75.
20.Papadaki HA,Boumpas DT,Gibson FM,et al.Increased apoptosis of bone marrow CD34+ cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus.Br J Haematol,2001,115:167-174.
21.徐婷,金鸥阳,赵盛楠,等.系统性红斑狼疮患者骨髓间充质干细胞多向分化能力异常.中华风湿病杂志,2009,13:185-186.
22.Zhou K,Zhang H,Jin O,et al.Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.Cell Mol Immunol.2008,5:417-24.
23.Rao M S,Mattson M P.Stem cells and aging:expanding the possibilities.Mech Ageing Dev,2001,122:713-734.
24.金鸥阳,张华勇,徐婷,等.青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制.实用临床医药杂志,2007,11:5-9.
1.孙凌云.自身免疫病-造血干细胞病.中华风湿病学杂志,2000,4:5-6.
2.张华勇,冯学兵,孙凌云.系统性红斑狼疮患者骨髓间质干细胞生物学特性及对造血支持的研究.中华风湿病学杂志,2006,6:331-334.
3.Kalia N,Pockley AG,Wood RF,et al.Effects of FK409 on intestinal ischemia-reperfusion injury and ischemia-induced changes in the rat mucosal villus microcirculation.Transplantation,2001,72:1875-1880.
4.Bras M,Queenan B,Susin SA.Programmed cell death via mitochondria:different modes of dying.Biochemistry,2005,70:231-239.
5.Qin ZH,GU ZL.Huntingtin processing in pathogenesis of Huntington disease.Acta Pharmacol Sin,2004,25:1243-1249.
6.Fridman R,Scott AF,Muller D,et al.The role of cell adhesion and migration in the in vitro invasiveness of mouse adkidney carcinoma cells.Invasion Metastasis,1990,10:208-214.
7.Kuroda N,Naruse K,Miyazaki E,et al.Vinculin:its possible use as a marker of normal collecting ducts and kidney neoplasms with collecting duct system phenotype.Mod Pathol,2000,13:1109-1114.
8.Kogan O,Yarden A,Gimona M,et al.Preliminary crystallographic study of turkey gizzard vinculin.Acta Crystallogr D Biol Crystallogr,2000,56:1055-1057.
9.Coll JL,Ben-Ze'ev A,Ezzell RM,et al.Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell morphology,adhesion,and locomotion.Proc Natl Acad Sci,1995,92:6161-6165.
10.Kawahara E,Tokuda R,Nakanishi I.Migratory phenotypes of Hsc-3 squamous carcinoma cell line induced by EGF and PMA:relevance to migration of loosening of adhesion an vinculin-associated focal contacts with prominent filopodia.Cell Biol Int,1999,23:163-174.
11.Perez M M,Jamora C,Fuchs E.Stickly business:orchestrating cellular singnals at adherens junctions.Cell,2003,112:535-548.
12.Geiger B,Volk T,Volberg T,et al.Molecular interactions in adherens-type contacts.J Cell Sci,1987,8:251-272.
13.荣明,石玉秀.纽蛋白在原代培养神经元的分布及其与神经元形态的相关性.中国组织化学与细胞化学杂志,2002,11:4-7.
14.Watanabe N,Ando K,Yoshida S,et al.Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium.Biochem Biophys Res commun,2002,294:1121-1129.
1.Andonopouls A P,Constantopoulos SH,Galanopoulou V,et al.Pulmonary of non-smokimg patients with systemic lupus.Chest,1988,94:312-315.
2.Ikehara S.New strategies for allogeneic BMT.Bone Marrow Transplantation.2003,32:S73-75.
3.Duffield JS,Bonventre JV.Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury.Kidney Int,2005,68:1956-1961.
4.Sun L Y,Zhang H Y,Feng X B,et al.Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus.Lupus,2007,16:121-128.
5.顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓间质干细胞超微结构及细胞骨架的特征.中华风湿病病学杂志,2008,12:397-400.
6.Rao M S,Mattson M P.Stem cells and aging:expanding the possibilities.Mech Ageing Dev,2001,122:713-734.
7.Atsushi Sadanaga,Hitoshi Nakashima,Kohsuke Masutani,et al.Amelioration of autoimmune nephritis by Imatinib in MRL/lpr mice.Arthritis Rheum,2005,12:3987-3996.
8.Hasegawa H,Inoue A,Muraoka M,et al.Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice.Arthritis Research Therapy,2007,9:R15-27.
9.Aggarwal S,Pittenger M F.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
10.Le Blanc K,Rasmusson I,Sundberg B,et al.Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.Lancet,2004,363:1439-1441.
11.Tse WT,Pendleton JD,Beyer WM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
12.Le BlancK,Tammik L,Rosendahl K,et al.HLA expression and immunologic properties of undifferentiated and differentiated mesenchymal stem cells.Exp Hematol,2003,31:890-896.
13.Shi M,Li J,Liao L,et al.Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment:role in homing efficiency in NOD/SCID mice.Haematologica,2007,92:897-904.
14.田兆方,杜江,王斌,等.人骨髓源性MSCs移植新生大鼠的实验研究.广东医学,2006,27:1461-1463.
15.颜小华,陈晓.脐血间充质干细胞静脉移植治疗新生大鼠缺血缺氧性脑损伤.中国新生儿科杂忐,2006,21:158-161.
16.Zhou K,Zhang H,Jin O,et al.Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.Cell Mol Immunol,2008,5:417-24.
17.孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11:2-5.
18.Plumas J,Chaperot L,Richard MJ,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19:1597-1604.
19.Togel F,Hu Z,Weiss K,et al.Administered mesenchymal stem cells protect against ischemic acute kidney failure through differentiation-independent mechanisms.Am J Physiol Kidney Physiol,2005,289:F31-F42.
20.Ninichuk V,Gross O,Segerer S,et al.Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice.Kidney Int,2006,70:121-129.
21.Rojas M,Xu J,Woods CR,et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol,2005,33:145-152.
22.Ortiz LA,Gambelli F,McBride C,et al.Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.PNAS,2003,100:8407-8411.
23.赵峰,李圣青,张宇飞,等.骨髓间充质干细胞在肺损伤大鼠肺组织的分化.解放军医学杂志,2007,32:131-133.
1.Giuseppe G,Loreto G,Ranieri E,et al.Monocyte chemoattractant peptide-1 expression in acute and chronic human nephritides apathogenetic role in interstitial monocytes recruitment.J Am Soc Nephrol,1996,7:906-913.
2.Wada T,Yokoyama H,Su SB,et al.Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.Kidney Int,1996,49:761-767.
3.Noris M,Bernasconi S,Casiraghi F,et al.Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.Lab Invest,1995,73:804-809.
4.Lima G,Soto-Vega E,Atisha-Fregoso Y,et al.MCP-1,RANTES,and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus.Hum Immunol,2007,68:980-985.
5.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein-1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
6.Bianchi ME,Beltrame M.Upwardly mobile proteins.Workshop:the role of HMG proteins in chromatin structure,gene expression and neoplasia.Embo Rep,2000,1:109-114.
7.Taniguchi N,Kawahara K,Yone K,et al.High mobility group box chromosomal protein 1 plays a role in pathogenesis of rheumatoid arthritis as a novel cytokine.Arthritis Rheum,2003,48:971-981.
8.Kokkola R,Sundberg E,Ulfgren AK,et al.High mobility group box chromosomal protein 1:a novel proinflammatory mediator in synovitis.Arthritis Rheum,2002,46:2598-2603.
9.Pullerits R,Jonsson IM,Verdrengh M,et al.High mobility group box chromosomal protein 1,a DNA binding cytokine,induces arthritis.Arthritis Rheum,2003,48:1693-1700.
10.Kokkola R,Li J,Sunberg E,et al.Successful treatment of collagen-induced arthritis in mice and rats by target in extracellular high mobility group box chromosomal protein 1 activity.Arthritis Rheum,2003,48:2052-2058.
11.Popovic K,EK M,Espinosa A,et al.Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus.Arthritis Rheum,2005,52:3639-3645.
12.周健光,蔡绥,郑敏.高迁移率族蛋白-1在狼疮性肾炎中的表达.中华医学会第十二次全国 皮肤性病学术会议论文集,2006:86.
13.陈荣权,陈香美,崔世维,等.明胶酶及其抑制物在衰老大鼠肾组织中的表达及意义.中国老年学杂志,2004,24:129-132.
14.蔡广研,陈香美,王兆霞,等.MRL/lpr狼疮小鼠肾脏明胶酶表达随增龄变化及意义.中华病理学杂志,2002,31:432-435.
15.Tveita AA,Rekvig OP,Zykova SN.Increased glomerular matrix metalloproteinase activity in murine lupus nephritis.Kidney Int,2008,74:1150-1158.
16.Fontenot JD,Gavin MA,Rudensky AY.Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells.Nat Immunol,2003,4:330-336.
17.赵盛楠,孙凌云.糖皮质激素对系统性红斑狼疮CD4~+Foxp3~+T细胞水平的影响.中华风湿病学杂志,2008,12:166-169.
18.Colotta F,Sciacca FL,Sironi M,et al.Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin.Am J Pathol,1994,144:975-985.
19.Maus U,Henning S,Wenschuh H,et al.Role of endothelial MCP-lin monocyte adhesion to inflamed human endothelium under physiological flow.Am J Physiol Heart Circ Physiol,2002,283:H2584-H2591.
20.Maslin CL,Kedzierska K,Webster NL,.et al.Transendothelial migration of monocytes:the underlying molecular mechanisms and consequences of HIV-1 infection.Curr HIV Res,2005,3:303-317.
21.Zoja C,Liu XU,Donadelli R,et al.Kidney expression of monocyte chemoattractant protein-1in lupus autoimmune mice.J Am Soc Nephrol.1997,8:720-729.
22.Adams DH,Shaws S.Leucocyte-endothelial interactions and regulation of leucocyte migration.Lancet,1994,343:831-836.
23.Wada T,Furuichi K,Segawa-Takaeda C,et al.MIP-lalpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.Kidney Int,1999,56:995-1003.
24.Tesch GH,Maifert S,Schwarting A,et al.Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.J Exp Med,1999,190:1813-1824.
25.Zoja C,Corna D,Benedetti G,et al.Bindarit retards kidney disease and prolongs survival in murine lupus autoimmune disease.Kidney Int,1998,53:726-734.
26.Hitoshi H,Masashi K,Miho S,et al.Antagonist of monocyte chemoattractant protein 1ameliorates the initiation and progression of lupus nephritis and kidney vasculitis in MRL/lpr mice.Arthritis & Rheum,2003,48:2255-2266.
27.Tse KC,Lam MF,Tang SC,et al.A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade.Lupus,2007,16:46-51.
28.Mok CC,Tong KH,To CH,et al.Tacrolimus for induction therapy of diffuse proliferative lupus nephritis:an open-labeled pilot study.Kidney Int,2005,68:813-817.
29.Lenz O,Contreras G.Treatment options for severe lupus nephritis.Arch Immunol Ther Exp,2004,52:356-365.
30.Politt D,Heintz B,Floege J,et al.Tacrolimus(FK506) based immunosuppression in severe systemic lupus erythematosus.Clin Nephrol,2004,62:49-53.
31.Maruyama M,Yamasaki Y,Sada K,et al.Good response of membranous lupus nephritis to tacrolimus.Clin Nephrol,2006,65:276-279.
32.Tam LS,Li EK,Wong CK,et al.Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy:an open label trial.Ann Rheum Dis,2006,65:417-418.
33.Degryse B,De Virgilio M.The nuclear protein HMGB-1,a new kind of chemokine? FEBS Lett,2003,553:11-17.
34.Yamamoto Y,Kato I,Doi T,et al.Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice.J Clin Invest,2001,108:261-268.
35.Pawar RD,Patole PS,Ellwart A,et al.Ligands to nucleic acid-specific toll-like receptors and the onset of lupus nephritis.J Am Soc Nephrol,2006,17:3365-2273.
36.Uesugi H,Ozaki S,Sobajima J,et al.Prevalence and characterization of novel pANCA,antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2,in systemic rheumatic diseases.J Rheumatol,1998,25:703-709.
37.Deocharan B,Zhou JJ,Antar K,et al.Alpha-actinin immunization elicits anti-chromatin autoimmunity in nonautoimmune mice.J Immunology,2007,179:1313-1321.
38.Stemmann-Niggh K,Ziswiler R,Kung M,et al.Inhibition of matrix metalloproteinases attenuates anti-Thy1 nephritis.J Am Soc Nephrol,1998,9:397-407.
39.McMillan JI,Riordan JW,Couser WG,et al.Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteninase-9 with enhanced expression in a model of membranous nephropathy.J Clin Invest,1996,97:1094-1101.
40.Nakamura T,Ebihara I,Tomino,et al.Effect of a specific endothelin A receptor antagonist on murine nephritis.Kidney Int,1995:51:481-489.
41.Lu LL,Liu YJ,Yang SG,et al.Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials.Haematologica,2006,91:1017-1026.
42.Shinizu A,Kitamura H,Masuda Y,et al.Apoptosis in the repair process of experimental proliferative glomerulonephritis.Kidney Int,1995,47:114-121.
43.Soto H,Mosquera J,Hemriquez La Roche C,et al.Apoptosis in proliferative glomerulonephritis:decreased apoptosis expression in lupus nephritis.Nephrol Dial Transplant,1997,12:273-280.
44.Lu F,Shen W,Zhang X,et al.Dysregulation of apoptosis:a possible mechanism leading to chronic progressive kidney histological changes in lupus nephritis.Chin Med J(Engl),2000,113:1082-1086.
45.王建中,廖洪军,陈香美,等.甲基泼尼松龙对狼疮小鼠肾脏细胞凋亡及ICE基因表达的影 响.中华内科学,1997,36:79-82.
46.孙秀珍,谢蜀生,龙振洲,等.青蒿素及其衍生物免疫抑制作用的实验研究.中西医结合杂志,1991,11:37-38.
47.仰锦虹,李道中.抗疟药蒿甲醚注射液对小鼠免疫功能的影响.广州中医学院学报,1990,7:102-105.
48.陈华,高玉祥.青蒿琥酯免疫作用机制的探讨.中华皮肤科杂志,1990,23:250-252.
49.郭兴伯,符林春,范太涛,等.青蒿琥酯静脉注射治疗脑型疟疾33例临床报告.广州中医学院学报,1993,9:1-3.
50.郭兴伯,符林春,简华香,等.健康人静脉注射青蒿琥酯的酎受性和毒副反应研究.中药新药与临床药理,1991,2:29.
51.钟嘉熙,刘亚敏,刘红姣,等.青蒿琥酯治疗系统性红斑狼疮的安全性观察.中药新药与临床药理,2000,11:336.
52.朱卫星,顾军.青蒿琥酯对狼疮样小鼠血清白细胞介素-6和转化生长因子-β的影响.中国麻风皮肤病杂志,2004,20:318-319.
53.徐丽敏,陈学荣.双氢青蒿素对狼疮性BXSB小鼠的作用.中国中西医结合皮肤性病学杂志,2002,1:19-20.
54.张剑勇,钟嘉熙.苓丹片,青蒿琥酯对SLE小鼠T淋巴细胞亚群的影响.中药药理与临床,1998,14:27-29.
55.张剑勇,钟嘉熙,彭胜权,等.苓丹片,青蒿琥酯对系统性红斑狼疮患者IL-2与sIL-2R 影响的研究.河南中医学院学报,2003,18:38-39.
56.董妍君,李卫东,屠呦呦,等.双氢青蒿素对BXSB狼疮小鼠自身抗体产生,TNFa分泌及狼疮性肾炎病理改变的影响.中国中西医结合杂志,2003,23:676-679.
57.董妍君,李卫东,屠呦呦,等.双氢青蒿素对BXSB小鼠狼疮肾炎的作用及机制研究.中国药理学通报,2003,19:1125-1128.
58.金鸥阳,张华勇,徐婷,等.青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制.实用临床医药杂志,2007,11:5-9.
1.Friendenstein AJ,Chailakhyan RK,Gerasimov UV.Bone marrow osteogenic stem cells:in vitro cultivation and transplantation in diffusion chambers.Cell Tissue Kinet,1987,20:263-272.
2.Majumdar MK,Keane-Moore M,Buyaner D,et al.Characterization and functionality of cell surface molecules on human mesenchymal stem cells.J Biomed Sci,2003,10:228-241.
3.Bogenrieder T,Herlyn M.Axis of evil:molecular mechanisms of cancer metastasis.Oncogene,2003,22:6524-6536.
4.Li Y,Hisha H,Inaba M,et al.Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection. Exp Hematol, 2000, 28: 950-960.
5. Krampera M, Cosmi L, Angeli R, et al. Role of IFN-g in the immunomodulatory activity of human mesenchymal stem cells. Stem Cells, 2005, 24: 386-98.
6. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol, 2002, 30: 42-48.
7. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 2003,102: 3837-3844.
8. Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol, 2003,31: 890-896.
9. Farrington-Rock C, Crofts NJ, Doherty MJ, et al. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation, 2004,110: 2226-32.
10. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone MinerRes. 2003, 18: 696-704.
11. Da Silva Meirelles L, Chagastelles PC. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci, 2006,119: 2204-2213.
12. Wexler SA, Donaldson C, Denning-Kendall P, et al. Adult bone marrow is a rich source of human mesenchymal stem cells but umbilical cord and mobilized adult blood are not. Br J Haematol, 2003, 121:368-374.
13. Kassem M, Kristiansen M, Abdallah BM. Mesenchymal stem cells:Cell biology and potential use in therapy. Pharmacol Toxicol, 2004, 95: 209-214.
14. Von Luttichau I, Notohamiprodjo M, Wechselberger A, et al. Human adult CD34-progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4. Stem Cells Dev, 2005,14: 329-336.
15. Lopez PA, Marais EA, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: Comparison of chemokine and growth factor chemotactic activities. Stem Cells, 2007, 25:1737-1745.
16. Schmidt A, Ladage D, Schinkothe T, et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells , 2006, 24: 1750-1758.
17. Fiedler J, Brill C, Blum WF, et al. IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Biochem Biophys Res Commun, 2006, 345: 1177-1183.
18. Neth P, Ciccarella M, Egea V, et al. Wnt signaling regulates the invasion capacity of human mesenchymal stem cells. Stem Cells, 2006, 24: 1892-1903.
19. Oliver JA, Maarouf O, Cheema FH, et al. The kidney papilla is a niche for adult kidney stem cells. J Clin Invest, 2004, 114: 795-804.
20. Plumas J, Chaperot L, Richard MJ, et al. Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia, 2005, 19: 1597-1604.
21. Ito T, Suzuki A, Imai E, et al. Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling. J Am SocNephrol, 2001,12: 2625-2635.
22. Duffield JS, Bonventre JV. Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int, 2005, 68: 1956-1961.
23. Morigi M, Imberti B, Zoja C, et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute kidney failure. J Am Soc Nephrol, 2004,15:1794-1804.
24. Lange C, Togel F, Ittrich H, et al. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute kidney failure in rats. Kidney Int, 2005, 68:1613-1617.
25. Kunter U, Rong S, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol, 2006,17: 2202-2212.
26. Ninichuk V, Gross O, Segerer S, et al. Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int, 2006, 70:121-129.
27. Zhou K, Zhang H, Jin O, et al. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol, 2008, 5: 417-424.
1.PittingerM,Mackay A,Beck S,et al.Multilineage potential of adult human mesenchymal stem cells.Science,1999,284:143-147.
2.Chen LB,Jiang XB,Yang L.Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells.Word J Gastroenterol,2004,10:3016-3020.
3.Chao KC,Chao KF,Fu YS,et al.Islet-like clusters derived from mesenchymal stem cells in wharton's jelly of the human umbilical cord for transplantation to control type 1 diabetes.PLoS ONE,2008,3:e1451.
4.Le Blanc K,Tammik L,Zetterberg E,et al.HLA-expression and immunologic properties of undifferentiated and differentiated mesenchymal stem cells.Exp Hematol,2003,31:890-896.
5.TseWT,Pendleton JD,BeyerWM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
6.Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by differentme chanisms.Exp Cell Res,2005,305:33-41.
7.Bartholomew A,Sturgeon C,SiatskasM,et at.Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.Exp Hemato,2002,30:42-48.
8.Jiang XX,Zhang Y,Liu B,et al.Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.Blood,2005,105:4120-4126.
9.Aggarwal S,Pittenger MF.Human mesenchymal stem cells modulate allogeneic immune cell responses.Blood,2005,105:1815-1822.
10.Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit the formation of cytotoxic lymphocytes(CTL),but not activated CTL or natural killer(NK) cells.Transplantation,2003,76:1208-1213.
11.Le Blanc K,Rasmusson I,Gotherstrom C,et al.Mesenchymal stem cells inhibit the expression of CD25(interleukin-2 receptor) and CD38 on phytohae magglutinin-activated lymphocytes.Scand J Immunol,2004,60:307-315.
12.Krampera M,Glennie S,Dyson J,et al.Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.Blood,2003,101:3722-3729.
13.Holz A,Brett K,Oldstone MB.Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes.J Clin Invest,2001,108:1749-58.
14.Szelachowska M,Kretowski A,Kinalska I.Increased in vitro interleukin-12 production by peripheral blood in high-risk IDDM first degree relatives.Horm Metab Res,1997,29:168-171.
15.Ozer G,Teker Z,Cetiner S,et al.Serum IL-1,IL-2,TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings.J Pediatr Endocrinol Metab,2003,16:203-210.
16.Campbell IL,Iscaro A,Harrison LC.IFN-gamma and tumor necrosis factor-alpha,Cytotoxicity to murine islets of Langerhans.J Immunol,1988,141:2325-2329.
17.Yoon JW,Jun HS,Santamaria P.Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells.Autoimmunity,1998,27:109-122.
18.Overbergh L,Decallonne B,Branisteanu DD,et al.Acute shock induced by antigen vaccination in NOD mice.Diabetes,2003,52:335-341.
19.H(u|¨)bner MP,Thomas Stocker J,Mitre E.Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3(+) regulatory T cells.Immunology.2008.[Epub ahead of print].
20.Kodama S,K(u|¨)htreiber W,Fujimura S,et al.Islet regeneration during the reversal of autoimmune diabetes in NOD mice.Science,2003,302:1223-1227.
21.李立人,徐青.骨髓基质干细胞移植对糖尿病大鼠血糖的影响.苏州大学学报,2005,25:584-585.
22.Wu T,Levay-Young B,Heuss N,et al.Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy.Transplantation,2002,74:22-27.
23.Ikebukuro K,Adachi Y,Yamada Y,et al.Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats.Transplantation,2002,73:512-518.
24.Lee RH,Seo MJ,Reger RL,et al.Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and kidney glomeruli in diabetic NOD/scid mice.Proc Natl Acad Sci U S A,2006,103:17438-17443.
25.顾志峰,金鸥阳,徐婷,等.脐带间质干细胞移植治疗MRL/lpr狼疮鼠的疗效.中华风湿病学杂志,2009,13:4-7.
26.顾志峰,金鸥阳,徐婷,等.脐带间质干细胞移植对MRL/lpr狼疮鼠间质性肺炎的影响.中华结核和呼吸杂志,2009,32:33-37.
1.王海颖.陈以平教授治疗狼疮性肾炎的经验.新中医,2001,33:9-10.
2.盛梅笑,王身菊.狼疮性肾炎中医临床证候分型的调研分析.江苏中医药,2004,25:12-14.
3.王维英.姚树锦治疗狼疮性肾炎经验介绍.陕西中医,2000,21:463-464.
4.姜兆荣,莫成荣.″毒损肾络″理论在狼疮性肾炎中的应用.中医药学刊,2004,22:1735-1735.
5.王欢,李继科,漆剑.艾儒棣教授治疗气阴两虚证狼疮性肾炎经验.四川中医,2007,25:2-3.
6.于伟,郑慧文.狼疮性肾炎中医病机与治法.浙江中医学院学报,1999,23:18-19.
7.王付民.活血化瘀治疗狼疮性肾炎.辽宁中医杂志,1994,21:454-455.
8.茅建春,苏励,顾军花,等.陈湘君治疗狼疮性肾炎的经验.辽宁中医杂志,2004,31:182-183.
9.刘玉宁,邓跃毅,王立红.陈以平教授治疗狼疮性肾炎的经验.中国中西医结合肾病杂志,2003,4:437-438.
10.曹惠芬,林丽.孟如教授治疗系统性红斑狼疮的经验.云南中医中药杂志,1999,20:1-3.
11.廖晨晖.狼疮性肾炎的中医治疗临床体会.中华实用中西医杂志,2000,1:2637-2638.
12.张世涛.何学红诊治狼疮性肾炎经验.实用中医药杂志,2007,23:377.
13.高景环,孟祥震.狼疮性肾炎临床诊治体会.天津中医药,2007,24:201-202.
14.史伟,唐爱华.中西医结合分阶段治疗狼疮性肾炎32例.现代中西医结合杂志,2000,9:1858-1860.
15.朱辟疆.狼疮性肾炎分型分阶段中西医结合治疗.中国中西医结合肾病杂志,2003,4:358-361.
16.米杰,孙素平.周翠英中西医结合治疗狼疮性肾炎经验.山东中医药大学学报,2006,30:316-317.
17.盛梅笑,王钢.狼疮性肾炎中医病机与治法探讨.中国中医基础医学杂志,2003,9:55-57.
18.李宝丽,庄鸿贤.狼疮性肾炎的病因病机及分期论治.山东中医杂志,2002,21:199-201.
19.阳晓,叶任高.38年中西医结合治疗肾脏病的临床和实验研究.中山医科大学学报,2000,21:401-408.
20.李春雯,金友,牛家臣.中西医结合治疗狼疮性肾炎临床观察.黑龙江中医药,2003,4:22.
21.杨林,成慧贞.中西医结合治疗狼疮性肾炎36例临床研究.河北中医,2003,25:698-700.
22.陈湘君,顾军花.复方自身清治疗活动性SLE的临床观察.上海中医药杂志,1999,16:18.
23.王萍,张广中,王禾,等.养阴益气解毒法治疗系统性红斑狼疮探讨.中国中西医结合皮肤性病学杂志,2003,2:79-82.
24.祁爱蓉,易铁钢,刘学耀,等.滋肾解毒活血中药对狼疮性肾炎系膜增殖的影响.广州中医 药大学学报,2007:24:104-108.
25.李相友,方敬爱.中西医结合治疗重症狼疮肾炎128例.中国医刊,2000,35:46-47.
26.母小真,陈湘君.补肾固精方治疗BXSB小鼠狼疮性肾炎的实验研究.上海中医药大学学报,2007,21:53-55.
27.李玉堂,刘学耀.中西医结合治疗难治性狼疮性肾炎18例.湖北中医杂志,2001,23:19.
28.眭书魁,李立.狼疮饮治疗系统性红斑狼疮的临床研究.河北中医,2000,22:85-89.
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