肾阳虚证和肾阴虚证血浆蛋白表达谱的比较研究
摘要
目的：中医“证”是疾病发生过程中不同阶段病因病机的高度概括,既然同一证有共同的临床表现和病理机制,那么其肯定有共同的物质基础,而这种物质基础很有可能反应在基因或蛋白水平上。肾所藏之精禀受于父母,是构成胚胎发育的原始物质,其与现代医学描述的遗传物质(DNA)具有一定的同一性。而基因又要在表达相应蛋白质的情况下才能影响生物的功能。蛋白组学是研究在生命体或细胞的整体水平研究蛋白质的表达和修饰状态,以及蛋白质与蛋白质的相互作用,从而确定人体的功能蛋白并阐明其在细胞中的功能与相互关系,揭示生命活动的本质。
肾阴虚证和肾阳虚证是中医学的基本证候,历代医家对肾阴虚证和肾阳虚证的理论与防治研究都颇为重视。肾阴虚证和肾阳虚证作为疾病的某一阶段的主要矛盾,必然受到“病”这一基本矛盾的影响。正是由于不同疾病的特异性,决定了不同疾病相同证侯之间的差异；而同一疾病不同中医证侯之间也存在差异。只有通过对这些差异的研究,进而归纳出证的一般规律,才有可能对肾阴虚证和肾阳虚证有更全面的解析。因此,“病证结合”是研究肾阴虚证和肾阳虚证差异蛋白表达的重要思路。
本研究采取“病证结合”的方法,以IgA肾病和亚健康状态的肾阴虚证和肾阳虚证为研究对象,对其各种细胞因子靶蛋白进行抗体芯片表达谱的比较研究,筛选肾阴虚证、肾阳虚证相关蛋白的改变,通过细胞信号转导等方面的研究,结合前期试验结果,寻找主要的细胞因子改变,为确定中医肾虚证证候客观化指标提供依据。
方法：1、采用“病证结合”的方法,选取确诊为IgA肾病和亚健康状态的肾阴虚证和肾阳虚证患者,作为实验组；选择健康志愿者作为正常对照组。
2、收集样本,制备样品,运用生物素直接标记技术,检测出多种细胞因子的表达水平,研究肾阴虚证和肾阳虚证的细胞因子改变。
结果：1、肾阴虚证组与正常对照组比较,获得差异表达蛋白共25条,其中表达水平上调的有2条(BMP5、TIMP4),表达水平下调的有23条(OSM、CXCR4、GCG、CXCR1、CTLA-4、Siglec-9、CCR7、IL-17A、IL-17F、TRADD、IGFBP-6、THBS2、IL-4R、HGFR、IL-RA、Osteoactivine、MMP10、M-CSF R、G-CSF R、CNTF、IL-17C、TGFβ、FGF23)。这些差异表达的蛋白按功能分析进行大体分类,主要涉及到免疫失调、新陈代谢、蛋白质生物合成、氧化应激、损伤修复、细胞凋亡、细胞信号传导有关等方面。肾阴虚证差异表达蛋白的异常变化,与中医肾阴虚证所表现的五心烦热、潮热盗汗、腰膝酸软、头晕目眩、易感外邪、精神萎靡、反应迟钝等症状相符。
2、肾阳虚证组与正常对照组比较,获得差异表达蛋白共14条(Csk、BMP5、Frizzled1、Frizzled4、BDNF、CXCR3、LBP、LTBP1、IL-27RA、M-CSF、L-13RαⅡ、PECAM-1、Activin RⅡA、FGF R5),表达水平均上调。主要涉及到免疫应答、新陈代谢、细胞凋亡、细胞黏附、损伤修复、氧化应激、生殖能力等方面。肾阳虚证差异表达蛋白的异常变化,与中医肾阳虚证所表现的腰膝酸软、发脱齿松、耳鸣耳聋、反应迟钝、手足发冷、性欲减退,男子阳痿早泄,女子宫寒不孕等症状相符。
3、肾阳虚证与肾阴虚证比较,共获得差异表达蛋白1条(BMP5),表达水平上调。主要涉及细胞凋亡、骨的合成等方面。中医认为,肾藏精,主人体的生长、发育和生殖,在体合骨,生髓。此共同蛋白的改变与中医理论相符。
4、中医认为：肾藏精,主人体的生长、发育和生殖,肾主水,主纳气,在体合骨,生髓。肾精气盛衰是机体生、长、壮、老、已的基石,同时又是人体全身阴阳的根本。通过比较分析,我们发现肾阴虚证与肾阳虚证存在明显的靶蛋白改变,主要涉及到免疫失调、新陈代谢、细胞周期、骨骼发育、DNA修复、蛋白质的合成、生殖能力、神经营养、造血功能等方面的功能,与中医基本理论相符。
结论：1、肾阴虚证与肾阳虚证差异表达蛋白存在明显不同,提示肾阴虚证与肾阳虚证有着各自不同的蛋白表达谱,这是符合中医理论的。同时,肾阴虚证与肾阳虚证差异表达蛋白可以为肾阴虚证和肾阳虚证的中医辨证分型提供科学依据。
2、肾阴虚证与肾阳虚证存在共同的差异表达蛋白,这表明肾阴虚证与肾阳虚证都存在肾虚的现象,这不但为研究中医证侯本质提供科学的思路与方法,也为探讨肾阴虚证和肾阳虚证在蛋白水平的发生机制奠定基础。
3、蛋白芯片是研究中医证候相关蛋白的比较理想的一种技术方法。从蛋白组学的角度探讨肾阴虚证与肾阳虚证,有利于揭示肾的本质。
Object:The syndrome of Traditional Chinese Medicine is the summarization of pathogenesis in different stages of diseases. Since the same symptom has common clinical manifestation and pathogenesis, then they have common material foundation, which will probably reflect in the gene or protein. The essence in Kidney, coming from the reproduction of the parents, is the basis of embryonic development and identity with DNA in modrn medicine. In the case of the corresponding proteins express can the gene affect its biological functions. Proteomics is the study of protein expression and modification status, and protein-protein interactions under the overall level of living organisms or cells, leading to determine the function of human proteins and to clarify its function in the cell and then revealed the nature of living.
Because the Kidney-yin deficiency and Kidney-yang deficiency is the basic syndrome of TCM, ancient physicians paid much more attentions on it. The Kidney-yin deficiency and Kidney-yang deficiency, which are the principal contradiction in a certain stage of a disease, must be influenced by the disease. The differences among varies diseases determined the differences among the same syndrome in varies diseases. Only when studied the differences and concluded the general rules can we analysis the Kidney-yin deficiency and Kidney-yang deficiency. As a result, "disease combined with syndrome" is an important ideas in studying the different proteins expression in the Kidney-yin deficiency and Kidney-yang deficiency.
Using "disease combined with syndrome" in this study, we took Kidney-yin deficiency and Kidney-yang deficiency as the research object to screen the changes of cytokine through antibody chips research. We look for a major change of cytokines, to provide the basis for the TCM Kidney deficiency syndrome for objective indicators.
Method:1 Using "disease combined with syndrome", selected the observers diagnosed with IgA nephropathy and subhealth condition, which are also in Kidney-yin deficiency and Kidney-yang deficiency, as the experimental group; choose healthy volunteers as the control group.
2 Afters the sample collection and preparation, using direct labeling of biotin technique to detect the expression of multiple cytokines, and study the cytokine changes of Kidney-yin deficiency and Kidney-yang deficiency.
Result:First,after the comparion between Kidney-yin deficiency group and normal control group, we received a total of 25 differentially expressed factors,2 of which are up(BMP5、TIMP4) and 23 are down(OSM、CXCR4、GCG、CXCR1、CTLA-4、Siglec-9、CCR7、IL-17A、IL-17F、TRADD、IGFBP-6、THBS2、IL-4R、HGFR、IL-RA、Osteoactivine、MMP10、M-CSFR、G-CSF R、CNTF、IL-17C、TGFβ2、FGF23). Classified by function, the differentially expressed factors mainly related to immune disorder, matabolism, protein biosynthesis, oxidative stress, damage repair, apoptosis, signal transduction and so on. The differentially expressed proteins in Kidney-yin deficiency conform to the theory of Kidney-yin deficiency of TCM, such as fever in chestpalms-soles, tidal fever and night sweating, lumbar debility, dizzy, susceptibility pericardium, listlessness, slow in reacting.
Secondly, after the comparion between Kidney-yang deficiency group and normal control group, we received a total of 14 differentially expressed factors, all of which are up(Csk、BMP5、Frizzled1、Frizzled4、BDNF、CXCR3、LBP、LTBP1、IL-27RA、M-CSF、L-13RαⅡ、PECAM-1、Activin RⅡA、FGF R5). Classified by function, the differentially expressed factors mainly related to immune response, metabolism, apoptosis, cell adhesion, damage repair, oxidative stress reproductive capacity and etc. The differentially expressed proteins in Kidney-yang deficiency conform to the theory of Kidney-yang deficiency of TCM, such as lumbar debility, hair off and tooth loose, tinnitus and deafness, slow in reacting, brothers chills, hyposexuality, man's impotence and premature ejaculation, woman's infertility due to uterus cold.
Thirdly, after the comparion between Kidney-yang deficiency group and Kidney-yin deficiency group, we received a total of 1 differentially expressed factors, of which is up(BMP5). Classified by function, the differentially expressed factors mainly related to apoptosis, bone synthesis and etc. TCM thought that Kidney stores essence, which is related to the body's growth, develepment and reproduction, and can compound the bone. The differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency conforms to the theory of Kidney deficiency of TCM.
Fourthly, TCM thought that the Kidney can store the essence, and is related to the body's growth, development and reproduction.The Kidney plays a main role in water metabolism and air lift, as well as the bone formation.The change of kindey essence is the cornerstone of the body's born,grow and old, which is also the base of yin and yang in the body. The differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency are mainly related to immune function, metabolism, cell cycle, bone development, DNA repair, protein synthesis, reproductive capacity, neurotrophic, and other aspects of hematopoietic function, of which are consistent with the basic theory of TCM.
Conclusion:Fistly, the differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency are great and clearly different, which is conform to the theory of TCM. The differentially expressed protein can also provide scientific evidence to the TCM syndrom differentiation.
Secondly, there are the same differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency, which can provide scientific ideas and methods in studying the essence of the TCM. It also plays an important role in studying the mechanism of Kidney-yang deficiency and Kidney-yin deficiency.
Thirdly, protein chip is an ideal method in the study of TCM-related protein. From the perspective of proteomics to study of Kidney-yang deficiency and Kidney-yin deficiency, we may reveal the essence of the kindey.
肾阴虚证和肾阳虚证是中医学的基本证候,历代医家对肾阴虚证和肾阳虚证的理论与防治研究都颇为重视。肾阴虚证和肾阳虚证作为疾病的某一阶段的主要矛盾,必然受到“病”这一基本矛盾的影响。正是由于不同疾病的特异性,决定了不同疾病相同证侯之间的差异；而同一疾病不同中医证侯之间也存在差异。只有通过对这些差异的研究,进而归纳出证的一般规律,才有可能对肾阴虚证和肾阳虚证有更全面的解析。因此,“病证结合”是研究肾阴虚证和肾阳虚证差异蛋白表达的重要思路。
本研究采取“病证结合”的方法,以IgA肾病和亚健康状态的肾阴虚证和肾阳虚证为研究对象,对其各种细胞因子靶蛋白进行抗体芯片表达谱的比较研究,筛选肾阴虚证、肾阳虚证相关蛋白的改变,通过细胞信号转导等方面的研究,结合前期试验结果,寻找主要的细胞因子改变,为确定中医肾虚证证候客观化指标提供依据。
方法：1、采用“病证结合”的方法,选取确诊为IgA肾病和亚健康状态的肾阴虚证和肾阳虚证患者,作为实验组；选择健康志愿者作为正常对照组。
2、收集样本,制备样品,运用生物素直接标记技术,检测出多种细胞因子的表达水平,研究肾阴虚证和肾阳虚证的细胞因子改变。
结果：1、肾阴虚证组与正常对照组比较,获得差异表达蛋白共25条,其中表达水平上调的有2条(BMP5、TIMP4),表达水平下调的有23条(OSM、CXCR4、GCG、CXCR1、CTLA-4、Siglec-9、CCR7、IL-17A、IL-17F、TRADD、IGFBP-6、THBS2、IL-4R、HGFR、IL-RA、Osteoactivine、MMP10、M-CSF R、G-CSF R、CNTF、IL-17C、TGFβ、FGF23)。这些差异表达的蛋白按功能分析进行大体分类,主要涉及到免疫失调、新陈代谢、蛋白质生物合成、氧化应激、损伤修复、细胞凋亡、细胞信号传导有关等方面。肾阴虚证差异表达蛋白的异常变化,与中医肾阴虚证所表现的五心烦热、潮热盗汗、腰膝酸软、头晕目眩、易感外邪、精神萎靡、反应迟钝等症状相符。
2、肾阳虚证组与正常对照组比较,获得差异表达蛋白共14条(Csk、BMP5、Frizzled1、Frizzled4、BDNF、CXCR3、LBP、LTBP1、IL-27RA、M-CSF、L-13RαⅡ、PECAM-1、Activin RⅡA、FGF R5),表达水平均上调。主要涉及到免疫应答、新陈代谢、细胞凋亡、细胞黏附、损伤修复、氧化应激、生殖能力等方面。肾阳虚证差异表达蛋白的异常变化,与中医肾阳虚证所表现的腰膝酸软、发脱齿松、耳鸣耳聋、反应迟钝、手足发冷、性欲减退,男子阳痿早泄,女子宫寒不孕等症状相符。
3、肾阳虚证与肾阴虚证比较,共获得差异表达蛋白1条(BMP5),表达水平上调。主要涉及细胞凋亡、骨的合成等方面。中医认为,肾藏精,主人体的生长、发育和生殖,在体合骨,生髓。此共同蛋白的改变与中医理论相符。
4、中医认为：肾藏精,主人体的生长、发育和生殖,肾主水,主纳气,在体合骨,生髓。肾精气盛衰是机体生、长、壮、老、已的基石,同时又是人体全身阴阳的根本。通过比较分析,我们发现肾阴虚证与肾阳虚证存在明显的靶蛋白改变,主要涉及到免疫失调、新陈代谢、细胞周期、骨骼发育、DNA修复、蛋白质的合成、生殖能力、神经营养、造血功能等方面的功能,与中医基本理论相符。
结论：1、肾阴虚证与肾阳虚证差异表达蛋白存在明显不同,提示肾阴虚证与肾阳虚证有着各自不同的蛋白表达谱,这是符合中医理论的。同时,肾阴虚证与肾阳虚证差异表达蛋白可以为肾阴虚证和肾阳虚证的中医辨证分型提供科学依据。
2、肾阴虚证与肾阳虚证存在共同的差异表达蛋白,这表明肾阴虚证与肾阳虚证都存在肾虚的现象,这不但为研究中医证侯本质提供科学的思路与方法,也为探讨肾阴虚证和肾阳虚证在蛋白水平的发生机制奠定基础。
3、蛋白芯片是研究中医证候相关蛋白的比较理想的一种技术方法。从蛋白组学的角度探讨肾阴虚证与肾阳虚证,有利于揭示肾的本质。
Object:The syndrome of Traditional Chinese Medicine is the summarization of pathogenesis in different stages of diseases. Since the same symptom has common clinical manifestation and pathogenesis, then they have common material foundation, which will probably reflect in the gene or protein. The essence in Kidney, coming from the reproduction of the parents, is the basis of embryonic development and identity with DNA in modrn medicine. In the case of the corresponding proteins express can the gene affect its biological functions. Proteomics is the study of protein expression and modification status, and protein-protein interactions under the overall level of living organisms or cells, leading to determine the function of human proteins and to clarify its function in the cell and then revealed the nature of living.
Because the Kidney-yin deficiency and Kidney-yang deficiency is the basic syndrome of TCM, ancient physicians paid much more attentions on it. The Kidney-yin deficiency and Kidney-yang deficiency, which are the principal contradiction in a certain stage of a disease, must be influenced by the disease. The differences among varies diseases determined the differences among the same syndrome in varies diseases. Only when studied the differences and concluded the general rules can we analysis the Kidney-yin deficiency and Kidney-yang deficiency. As a result, "disease combined with syndrome" is an important ideas in studying the different proteins expression in the Kidney-yin deficiency and Kidney-yang deficiency.
Using "disease combined with syndrome" in this study, we took Kidney-yin deficiency and Kidney-yang deficiency as the research object to screen the changes of cytokine through antibody chips research. We look for a major change of cytokines, to provide the basis for the TCM Kidney deficiency syndrome for objective indicators.
Method:1 Using "disease combined with syndrome", selected the observers diagnosed with IgA nephropathy and subhealth condition, which are also in Kidney-yin deficiency and Kidney-yang deficiency, as the experimental group; choose healthy volunteers as the control group.
2 Afters the sample collection and preparation, using direct labeling of biotin technique to detect the expression of multiple cytokines, and study the cytokine changes of Kidney-yin deficiency and Kidney-yang deficiency.
Result:First,after the comparion between Kidney-yin deficiency group and normal control group, we received a total of 25 differentially expressed factors,2 of which are up(BMP5、TIMP4) and 23 are down(OSM、CXCR4、GCG、CXCR1、CTLA-4、Siglec-9、CCR7、IL-17A、IL-17F、TRADD、IGFBP-6、THBS2、IL-4R、HGFR、IL-RA、Osteoactivine、MMP10、M-CSFR、G-CSF R、CNTF、IL-17C、TGFβ2、FGF23). Classified by function, the differentially expressed factors mainly related to immune disorder, matabolism, protein biosynthesis, oxidative stress, damage repair, apoptosis, signal transduction and so on. The differentially expressed proteins in Kidney-yin deficiency conform to the theory of Kidney-yin deficiency of TCM, such as fever in chestpalms-soles, tidal fever and night sweating, lumbar debility, dizzy, susceptibility pericardium, listlessness, slow in reacting.
Secondly, after the comparion between Kidney-yang deficiency group and normal control group, we received a total of 14 differentially expressed factors, all of which are up(Csk、BMP5、Frizzled1、Frizzled4、BDNF、CXCR3、LBP、LTBP1、IL-27RA、M-CSF、L-13RαⅡ、PECAM-1、Activin RⅡA、FGF R5). Classified by function, the differentially expressed factors mainly related to immune response, metabolism, apoptosis, cell adhesion, damage repair, oxidative stress reproductive capacity and etc. The differentially expressed proteins in Kidney-yang deficiency conform to the theory of Kidney-yang deficiency of TCM, such as lumbar debility, hair off and tooth loose, tinnitus and deafness, slow in reacting, brothers chills, hyposexuality, man's impotence and premature ejaculation, woman's infertility due to uterus cold.
Thirdly, after the comparion between Kidney-yang deficiency group and Kidney-yin deficiency group, we received a total of 1 differentially expressed factors, of which is up(BMP5). Classified by function, the differentially expressed factors mainly related to apoptosis, bone synthesis and etc. TCM thought that Kidney stores essence, which is related to the body's growth, develepment and reproduction, and can compound the bone. The differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency conforms to the theory of Kidney deficiency of TCM.
Fourthly, TCM thought that the Kidney can store the essence, and is related to the body's growth, development and reproduction.The Kidney plays a main role in water metabolism and air lift, as well as the bone formation.The change of kindey essence is the cornerstone of the body's born,grow and old, which is also the base of yin and yang in the body. The differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency are mainly related to immune function, metabolism, cell cycle, bone development, DNA repair, protein synthesis, reproductive capacity, neurotrophic, and other aspects of hematopoietic function, of which are consistent with the basic theory of TCM.
Conclusion:Fistly, the differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency are great and clearly different, which is conform to the theory of TCM. The differentially expressed protein can also provide scientific evidence to the TCM syndrom differentiation.
Secondly, there are the same differentially expressed protein in Kidney-yang deficiency and Kidney-yin deficiency, which can provide scientific ideas and methods in studying the essence of the TCM. It also plays an important role in studying the mechanism of Kidney-yang deficiency and Kidney-yin deficiency.
Thirdly, protein chip is an ideal method in the study of TCM-related protein. From the perspective of proteomics to study of Kidney-yang deficiency and Kidney-yin deficiency, we may reveal the essence of the kindey.
引文
[1]魏敏.肾阴虚证和肾阳虚证基因表达谱的比较研究[D].南方医科大学,2009.
[2]高博,尹桂山.Effect of tonifying kidney recipes on the protein kinase activity in hypothalamus of Kidney-yang-deficient rat[J].中国中医基础医学杂志,2000(01).
[3]曲耀华,刘彬,厉永强.补肾方剂对大鼠成骨样细胞增殖及相关酶类的影响[J].山东中医杂志,2003(07).
[4]高博,尹桂山.补肾药对肾阳虚大鼠下丘脑组织蛋白激酶活性的影响[Z].2000：6,30-33.
[5]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca-(2+)-Mg-(2+)-ATP酶活性影响的实验研究[J].中国骨质疏松杂志,1997(03).
[6]郑洪新,崔家鹏,刘景峰,等.肾虚骨质疏松症病理机制及补肾方药对其防治作用的实验研究[J].中国医药学报,1998(04).
[7]刘彬,皇甫超申,房娜.中药补肾方剂对大鼠骨肉瘤细胞增殖及相关酶活性的影响[J].第四军医大学学报,2006(03).
[8]沈自尹.衰老—生理性肾虚证的HPAT轴分子网络调控研究[J].中国中西医结合杂志,2004(09).
[9]胡聪,曾祥国.试论“肾充于脑”的物质基础[J].长春中医学院学报,1997,13(1)：1-3.
[10]江明,李庆阳,严桂珍.老年脾、肾虚与SOD、LPO关系探讨[J].长春中医学院学报,2000(04).
[11]江明,李庆阳,郑旭.老年脾、肾虚与SOD关系研究[J].安徽中医学院学报,1999(06).
[12]陈扬荣,江明,李庆阳.老年脾肾虚证LPO、SOD、血脂关系的探讨[J].中国中医基础医学杂志,2002(07).
[13]李庆阳,江明,严桂珍.老年脾肾虚证LPO、SOD、血脂及细胞免疫水平变化[J].福建中医学院学报,2001(03).
[14]刘华,周君富.老年人生理性肾虚潜在性血瘀证红细胞SODA与LPO的研究[J].现代中西医结合杂志,1997(02).
[15]姚明忠,赵伟康.A β诱导海马神经元调亡的机制及补肾方的调控作用[J].中国老年学杂志,2001,21(6)：450-452.
[16]陈洁文,王勇.巴戟素补肾健脑作用的神经活动基础[J].广州中医药大学学报,1999,16(4)：314-317.
[17]戴薇薇,金国琴,张学礼,等.补肾方药对衰老大鼠海马学习记忆相关基因BDNF及其受体TrkB mRNA表达的影响[J].中华中医药杂志,2008,23(4)：296-299.
[18]于文涛,张一听,吴中秋,等.补肾活血方对血管性痴呆小鼠行为学及脑海马自由基代谢的影响[J].中国老年学杂志,2009(12)：1478-1480.
[19]赵传康,李文.固真方对老年大鼠海马和下丘脑—垂体—肾上腺—胸腺轴作用的研究[J].中医杂志,1995,36(5)：300-302.
[20]冯新玲,周安方,田代志,等.恐伤孕鼠对其仔鼠大脑海马区细胞凋亡的影响[J].光明 中医,2008,23(8)：1079-1081.
[21]冯新玲,周安方,郑三一.恐伤孕鼠对其仔鼠大脑海马区乙酰胆碱代谢的影响[J].中医药信息,2009,26(3)：68-69.
[22]周慎,陈立峰,周重余,等.滋肾、温肾、活血三法对老龄小鼠海马区神经细胞密度的影响[J].中国老年学杂志,2006,26(3)：392-393.
[23]赵新永,金国琴,顾翠英,等.左归丸和右归丸对皮质酮所致大鼠海马神经细胞病理模型学习记忆相关信号转导分子mRNA表达的影响[J].中国老年学杂志,2010,30(5)：622-625.
[24]蒋淑君,崔存德,许兰芝.肾阳虚大鼠下丘脑-垂体-性腺轴钙调蛋白的基因表达及补肾中药的调整作用[J].中国临床康复,2004,8(24)：5056-5057.
[25]沈皓,蔡德培,陈伯英.补肾中药对下丘脑-垂体促性腺机能的影响[J].中西医结合学报,2004,2(1)：53-57.
[26]赵玉霞,孔令钧,等.补肾合剂对绝经后女性性激素及血脂代谢的影响[J].辽宁中医杂志,2001,28(9)：537-538.
[27]赖远征,冯冰虹,刘美珍,等.补肾活血方对更年期大鼠性激素的影响[J].辽宁中医杂志,2004,31(1)：78-79.
[28]李富宏,张西民,王桂花,等.补肾活血中药对女性激素的影响——附36例临床疗效观察[J].中华实用中西医杂志,2004,17(15)：2386-2387.
[29]张霞,吴连荣.从肾虚和性激素角度探讨老年糖尿病冠心病[J].辽宁中医杂志,2003,30(3)：207.
[30]毕会民,肖万泽.男性肾阳虚糖尿病性激素水平测定及临床意义[J].辽宁中医杂志,1997,24(10)：438.
[31]严炜.女性围绝经期综合征中医证型与性激素关系的研究[J].福建中医学院学报,2004,14(3)：1-4.
[32]郭瑞林,赵宁侠,等.吸毒对细胞免疫、自由基、性激素的影响及与中医肾虚的关系[J].第四军医大学学报,2002,23(14)：1312-1314.
[33]李灿东,高碧珍,兰启防,等.原发性不孕症中医辨证分型与性激素水平的相关性研究[J].中医杂志,2005,46(3)：216-218.
[34]王非,王平,郑杨,等.择时服用右归丸对肾阳虚大鼠性激素水平的影响[J].中国中医药科技,2006,13(6)：374.
[35]张树成,吴志奎.补肾生血和补肾调经方药促血管生成作用实验研究[J].中医杂志,2000,41(6)：369-370.
[36]张树成,沈明秀.补肾生血和补肾调经方药对老龄雌性金黄地鼠生殖器官组织形态的影响[J].中国民间疗法,1998,6(5)：56-57.
[37]马惠荣,杜惠兰,宋翠淼,等.补肾调经方对雄激素诱导无排卵大鼠氧化损伤、抗氧化能力及卵巢雌激素水平的影响[J].中药药理与临床,2004,20(5)：34-36.
[38]马惠荣,杜惠兰,杨秀芳,等.补肾调经方对雄激素致不孕大鼠卵巢组织抗氧化的实验研究[J].中华中医药杂志,2005,20(4)：252-253.
[39]杜惠兰,宋翠淼,马惠荣,等.补肾调经方对雄激素致不孕大鼠子宫一氧化氮、血清睾酮的影响[J].中成药,2007,29(2)：284-285.
[40]宋翠淼,杜惠兰,马爱蕊,等.补肾调经方对雄激素致不孕大鼠子宫转化生长因子β1 及其受体的影响[J].中成药,2007,29(5)：652-655.
[41]宋翠淼,杜惠兰,马惠荣,等.补肾调经方对雄激素致无排卵大鼠卵巢转化生长因子β1及其受体表达的影响[J].中国医科大学学报,2006,35(6)：600-602.
[42]王金萍.补肾调经方加减治疗崩漏80例临床观察[J].中外医疗,2009,28(34)：111.
[43]张树成,张志洲,等.补肾调经方调经促排卵健内膜作用的临床实验研究[J].中医药学刊,2002,20(6)：720-721.
[44]丛日杰.中西医结合治疗顽固性肾病水肿[J].内蒙古中医药,2010,29(3)：56.
[45]孙红,张燕.中西医结合治疗糖尿病肾病水肿疗效观察[J].中国中医药信息杂志,2008(S1).
[46]陈爱玲,李雷.金匮肾气汤加减治疗特发性水肿42例[J].河南中医,2008,28(6)：18-19.
[47]杨毅勇,桑志平,王娟娟.健脾补肾、补锌治疗不明原因水肿[J].中国中医药咨讯,2010(13)：282.
[48]覃正壮.防己黄芪汤治疗原发性肾病综合征水肿期疗效观察[J].吉林中医药,2010,30(7)：582-583.
[49]罗仁,成玉斌,等.“小四五汤”治疗糖尿肾病疗效与ACE基因相关性研究[J].上海中医药大学学报,2001,15(1)：24-26.
[50]薛耀明,成玉斌,周琳,等.Ⅰ型血管紧张素Ⅱ受体基因多态性与2型糖尿病肾病的相关研究[J].中华内科杂志,2001(3)：173-175.
[51]周琳,罗仁,等.ACE基因的插入／缺失多态性与2型糖尿病伴高血压的相互关系[J].第一军医大学学报,2002,22(9)：808-810.
[52]郭奕斌,吕英,蔡浩武,等.广东肾虚型哮喘病ACE基因的遗传多态性[J].中国优生与遗传杂志,2006,14(8)：20-22.
[53]成玉斌,罗仁,薛耀明,等.肾虚型DN与AGT及AGTIR基因多态性关系的研究[J].现代中西医结合杂志,2003,12(22)：2387-2388.
[54]成玉斌,罗仁,等.肾虚型糖尿病肾病与Ⅰ型血管紧张素Ⅱ受体基因多态性相关性研究[J].新中医,2003,35(1)：36-37.
[55]薛耀明,成玉斌,等.血管紧张素Ⅰ转换酶基因多态性与2型糖尿病肾病的易感性及病情发展的相关研[J].第一军医大学学报,2001,21(2)：85-87.
[56]高振,阿地力江·阿布力米提,哈木拉提·吾甫尔.哮喘的下丘脑-垂体-肾上腺轴紊乱及中医药介入的影响[J].实用医学杂志,2008,24(11)：1855-1856.
[57]解玉,杨子珍,柴柏春.上海市哮喘儿童与β2-肾上腺素能受体基因多态性的关系[J].实用儿科临床杂志,2008,23(4)：272-273.
[58]许建华,吴敦序,等.不同补肾法对哮喘大鼠肺组织β2肾上腺素能受体]mRNA的影响[J].上海中医药大学学报,2001,15(3)：38-40.
[59]包照日格,吴敦序.补肾健脾中药对哮喘模型大鼠肺组织β—肾上腺素能受体及cAMP的影响[J].中药新药与临床药理,2000,11(2)：98-100.
[60]石晓兰.β肾上腺素能受体和糖皮质激素受体与哮喘的关系及中医药对其作用的研究[J].河南中医,2005,25(4)：83-86.
[61]王明明,项晓人,徐建亚.补肺益肾方对幼龄哮喘豚鼠肺内嗜酸粒细胞凋亡和IL-5受体表达的影响[J].医学研究生学报,2010,23(7)：697-699.
[62]黄璧璇,张素玲,许新连.补肾纳气汤对儿童哮喘缓解期气道炎症影响的研究[J].现代医院,2009,9(7)：65-66.
[63]罗凤鸣,何成奇,等.加味肾气丸对支气管哮喘气道炎症抑制作用的临床研究[J].福建中医学院学报,2001,11(2)：13-14.
[64]张荣华,彭勇,杨丽,等.益骨胶囊对去卵巢骨质疏松大鼠血清PTH、KCT的影响[J].四川中医,2005,23(11)：37-38.
[65]陈津岩,李志强,何赞厚,等.右归丸对肾阳虚证大鼠激素水平变化的影响[J].中外健康文摘：医药月刊,2008,5(4)：44-46.
[66]张荣华,彭柯萍,朱晓峰,等.益骨胶囊含药血清对大鼠成骨细胞雌激素受体mRNA及其蛋白表达的影响[J].中国中西医结合杂志,2005,25(4)：333-337.
[67]林一峰,魏合伟,蔡桦,等.骨康及其含药血清中类性激素样物质含量的测定[J].中医药学刊,2003,21(5)：663-664.
[68]孔维萍,阎小萍.补肾强督法对强直性脊柱炎患者骨密度、骨代谢影响的临床研究[J].新中医,2008,40(10)：36-38.
[69]李楠,王和鸣,郭素华,等.巴戟天多糖及其水提取物对体外培养成骨细胞活性的影响[J].中国组织工程研究与临床康复,2007,11(23)：4570-4572.
[70]李楠,王和鸣,林旭,等.巴戟天对成骨细胞生物学特性影响的实验研究[J].中国医药学报,2004(12).
[71]李楠,王和鸣,郭素华,等.巴戟天多糖对体外培养成骨细胞核心结合因子α1mRNA表达的影响[J].中华中医药杂志,2007,22(8)：517-519.
[72]李楠,王和鸣,郭素华,等.巴戟天多糖含药血清对体外培养成骨细胞凋亡的保护作用观察[J].中国骨伤,2008,21(1)：39-41.
[73]陈亚琼,黄艳红,吴维光,等.补肾中药醇提活性部位对成骨细胞Cbfal基因表达的影响[J].武警医学院学报,2005(06).
[74]魏义勇,石印玉,詹红生,等.补肾中药对成骨细胞VDR, Cbfα 1mRNA表达的影响[J].中国骨伤,2006(11).
[75]魏义勇,石印玉,詹红生.补肾中药对成骨细胞维生素D受体与核心结合因子α1蛋白表达的影响[J].上海中医药杂志,2005(11).
[76]魏义勇,周琦,石印玉,等.补肾中药对老龄成骨细胞VDR基因表达的研究[J].中国中医骨伤科杂志,2006(04).
[77]尚德阳,郑洪新,宗志宏,等.补肾中药对肾虚骨质疏松症大鼠肾组织中Smurf2的mRNA和蛋白表达影响研究[J].中华中医药学刊,2008(08).
[78]魏义勇,石印玉,冯伟,等.补肾中药对增龄成骨细胞VDR蛋白表达的影响[J].中国骨质疏松杂志,2006(02).
[79]王巍巍,魏义勇,石印玉.补肾中药对增龄大鼠成骨细胞Cbfα_1表达的影响[J].中国中医药信息杂志,2007(11).
[80]李娟,吴贺勇,唐井钢.补肾中药骨灵丸对成骨细胞矿化功能及骨桥蛋白基因表达的影响[J].热带医学杂志,2006(01).
[81]夏远军,沈霖,谢晶,等.补肾中药密骨片对成骨细胞生长因子转化生长因子β1mRNA表达的影响(英文)[J].中国临床康复,2006(11).
[82]王玲巧,李恩.补肾方药对氢醌诱发的背毛脱色小鼠酶的活性影响[J].中国中西医结合杂志,1999,19(S1)：99-100.
[83]孙爱华,李津婴.补肾法为主治疗内耳疾病的思路与方法[J].中医杂志,1998,39(5)：305-307.
[84]孙爱华,李津婴.从缺铁肾虚大鼠耳蜗显微结构与生理功能变化探讨肾与耳联系的物质基础[J].中医研究,1993,6(3)：14-17.
[85]孙爱华,王正敏.肾主耳理论的生化物质基础：缺铁大鼠肾虚...[J].中医杂志,1991,32(3)：44-46.
[86]刘鲁明,鞠远秀,高季珍,等.试从钙磷代谢角度探讨肾虚耳鸣的物质基础——56例肾虚患者临床观察[J].中西医结合杂志,1986,6(9)：538-539.
[87]王彤.基于时藏理论的"肾主骨"与细胞信号转导相关性研究[D].北京：北京中医药大学,2007.
[88]刘晓燕,郭霞珍,等.中医“肾应冬”调控机制与下丘脑G蛋白关系的研究[J].中国医药学报,2002,17(11)：660-662.
[89]刘晓燕,郭霞珍,刘燕池,等.“肾应冬”与性腺轴相关性的研究[J].中国医药学报,2003,18(9)：522-524.
[90]郭霞珍."肾应冬"生理机制的研究[J].中华中医药杂志,2004(z1)：74-76.
[91]沈自尹.肾的研究(续集)[M].上海：上海科学技术出版社,1990.313.
[92]沈自尹.肾的研究进展与总结[J].中华中医药杂志,1988(02).
[93]方素钦,林炳辉,叶盈,等.中老年人肾虚证与性激素及免疫功能的研究[J].福建中医药,2002(02).
[94]田鄂华,俞金秀.肝郁脾虚证酶学指标的初步探讨[J].湖北中医杂志,1989(3)：43-44.
[95]宋春风.肾阳虚大鼠下丘脑-垂体-靶腺轴超微结构和Ca<\'2+>.CaM信号系统的改变及补肾中药的调整作用[D].河北医科大学,2000.
[96]宋春风,尹桂山,李恩,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴FOs蛋白表达的影响[J].中国中医基础医学杂志,2001,7(10)：36-37.
[97]宋春风,尹桂山,孙素菊,等.右归饮对肾阳虚大鼠下丘脑-垂体-肾上腺轴钙调素mRNA表达的影响[J].中国中医基础医学杂志,2001,7(3)：20-23.
[98]宋春风,尹桂山,赵建宏,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴CaMPKII的影响[J].中国中医基础医学杂志,2001,7(8)：45-47.
[99]宋春风,郑师陵,吕佩源,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴、血淋巴细胞Ca2+和血清钙的影响[J].中国中医基础医学杂志,2002,8(5)：34-36.
[100]郭凯,徐蓉,俞伟,等.金匮肾气丸对肾阳虚动物模型影响的拆方研究[J].中医药学报,2003,31(1)：20-21.
[101]金国琴,赵伟康.补肾药延缓老年大鼠下丘脑—垂体—甲状腺轴的功能退化[J].标记免疫分析与临床,1998,5(1)：32-35.
[102]青姚,张志哲.肾阳虚患者甲状腺激素水平变化及温补肾阳的疗效观察[J].广西中医学院学报,2001,4(4)：63-64.
[103]杨丹丹,詹臻.温肾补阳方对实验性免疫低下小鼠胸腺免疫细胞分化影响的实验研究[J].江苏中医药,2005,26(3)：51-53.
[104]徐卫东,陆平成.补肾复方对胸腺细胞增殖周期、胸腺一氧化氮及抗氧化作用的影响[J].浙江中医药大学学报,2007(6)：693-694.
[105]张玲娟,沈自尹.补肾益气法对淋巴细胞糖皮质激素受体老年性改变的影响[J].中西医结合杂志,1990,10(10)：583-585.
[106]詹秀琴.补肾方药对老年大鼠胸腺细胞糖皮质激素受体的作用研究[J].南京中医药大学学报,2000,16(3)：152-153.
[107]秦路平,石汉平.蛇床子香豆素对肾阳虚模型大鼠学习记忆和神经肽的影响[J].第二军医大学学报,1997,18(2)：147-149.
[108]陈小峰,王培训,李道中.肾虚患者的自然杀伤细胞活性研究[J].中国中西医结合杂志,1989(07).
[109]陈小峰,许少峰.肾虚患者的细胞因子研究[J].福建中医学院学报,2000,10(2)：12-13.
[110]陈小峰,许少锋.肾与白细胞介素的关系——附28例肾虚患者的临床研究[J].中国中医基础医学杂志,2000(12).
[111]陈瑜,沈自尹,郭为民.老年大鼠T细胞凋亡相关基因表达模式的研究[J].中国老年学杂志,2002(05).
[112]范国荣,王晓玲.老年人肾虚证的T细胞亚群及对免疫调控的影响[J].中国中西医结合杂志,1992,12(8)：478-479.
[113]华碧春,陈小峰,杜建,等.补肾B方对老龄SD大鼠细胞因子表达的调节作用[J].中华中医药学刊,2008(06).
[114]华碧春,陈小峰,郑良朴,等.补肾A方对老龄SD大鼠细胞因子表达的调节作用[J].光明中医,2008(07).
[115]江明,李奕棋,李庆阳.老年脾、肾虚与细胞免疫关系研究[J].中国医药学报,2000(05).
[116]李庆阳,郑家铿.老年肾虚与T细胞亚群关系[J].福建中医学院学报,2001(02).
[117]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探[J].福建医药杂志,2000(S1).
[118]沈自尹,郭为民,陈瑜.补肾方对老年人T细胞凋亡相关基因群转录的调控模式研究[J].中国老年学杂志,2002(04).
[119]宋淑霞,蔡月花,李杰,等.益气补肾方药对老年小鼠T细胞凋亡及凋亡相关基因表达的影响[J].中华老年医学杂志,2003(04).
[120]宋淑霞,冯旭,蔡月花,等.益气补肾药方对老龄小鼠T细胞中NF-κB活性的影响及作用机制[J].细胞与分子免疫学杂志,2004(02).
[121]宋淑霞,吕占军,等.益气补肾方药对肾虚小鼠细胞因子IL—2、IL—2及IL--12基因表达的影响[J].中国实验动物学报,2002,10(2)：101-104.
[122]宋淑霞,吕占军,刘福英.益气补肾方药对肾虚小鼠脾细胞CD40、CD40L表达的调节[J].中华老年医学杂志,2002(05).
[123]杨嘉珍.肾虚血瘀证与红细胞免疫的关系[J].湖北中医杂志,1996(03).
[124]张文彭,王巍,等.老年肾虚证血浆过氧化脂质高密度脂蛋白胆固醇及其亚组分水平变化[J].中医杂志,1989,30(2)：43-46.
[125]陈晏珍,江家贵,等.肾虚与超氧化物歧化酶关系初探[J].中医杂志,1989,30(4)：42-43.
[126]江明,李庆阳,郑旭.老年脾肾虚与LPO关系研究[J].陕西中医学院学报,1999(05).
[127]冯端浩,刘洪尊,等.脾虚和肾虚小鼠模型红细胞膜流动性的变化[J].广州中医药大学学报,2003,20(1)：21-24.
[128]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca-(2+)-Mg-(2+)-ATP酶活性影响的实验研究[J].中国骨质疏松杂志,1997(03).
[129]郭金瑞,严惠芳.慢性肾炎唾液Na+、K+红细胞变形能力改变与肾阴虚证相关性研究[J].中医药学刊,2003,21(11)：1900-1901.
[130]陈德珍,管学忠.脾肾阴虚证患者血清铜锌含量的变化[J].辽宁中医杂志,1999,26(7)：291.
[131]马威,管竞环.用血液微量元素观察右归丸治疗肾阳虚证的实验研究[J].微量元素与健康研究,1999,16(2)：39-42.
[132]马正立,施玉华.填精补肾中药对老年大鼠下丘脑—垂体—性腺—胸腺轴的形态学研究[J].中医杂志,1989,30(8)：45-48.
[133]周锦鹏,徐凤仙.补肾中药对老年大鼠胸腺作用的光镜和电镜观察[J].上海中医药杂志,1994(4)：43-45.
[134]高岗.肾虚证代谢组学及六味地黄汤的干预研究[D].第二军医大学,2009.
[135]魏敏.肾阴虚证和肾阳虚证基因表达谱的比较研究[D].南方医科大学,2009.
[136]成玉斌,罗仁,薛耀明,等.肾虚型DN与ACE基因多态性相关研究[J].中国中医基础医学杂志,2002(05).
[137]成玉斌,罗仁,薛耀明,等.肾虚型DN与AGT及AGT1R基因多态性关系的研究[J].现代中西医结合杂志,2003,12(22)：2387-2388.
[138]成玉斌,罗仁,薛耀明,等.肾虚型糖尿病肾病与Ⅰ型血管紧张素Ⅱ受体基因多态性相关性研究[J].新中医,2003(01).
[139]Lim C S, Kim Y S, Chae D W, et al. Association of C-509T and T869C polymorphisms of transforming growth factor-betal gene with susceptibility to and progression of IgA nephropathy.[J]. Clin Nephrol,2005,63(2):61-67.
[140]钟逸斐,陈以平,邓跃毅.增生为主IgA肾病阴虚证与TGF-β1基因启动子区C-509T的相关性研究[J].湖北中医学院学报,2008(02).
[141]Miyata T, Nangaku M, Suzuki D, et al. A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy.[J]. J Clin Invest,1998,102(4):828-836.
[142]钟逸斐,陈以平,邓跃毅,等Megsin基因E1-5’UTR区A267G与免疫球蛋白A型肾病阴虚证的相关性[J].中西医结合学报,2008,6(5)：463-467.
[143]杨进,郭聂涛,李燕林,等.原发性肾病综合征中医辨证分型与红细胞CRl密度相关基因及数量表达和黏附活性的相关性[J].中国中西医结合肾病杂志,2005,6(3)：167-168.
[144]温成平,谢志军,宋平,等.系统性红斑狼疮中医证型与人类白细胞Ⅱ类抗原DR基因表达关系的研究[J].中国中西医结合杂志,2008(06).
[145]郑平东,肖黎,何立群,等.补肾方式经对IgA肾病肾虚证人群bcl—2基因表达变化的影响[J].中华国际医学杂志,2003,3(3)：210-212.
[146]孙伟正,赵淑英,等.慢性再生障碍性贫血中医辨证与HLA基因相关性研究[J].中国医药学报,2002,17(3)：167-169.
[147]孙伟正,杨东光,刚宏林.慢性再生障碍性贫血中医辨证分型与MHC—DRB1*等位 基因的相关性研究[J].中医杂志,2004,45(6)：450-452.
[148]赵晓山,罗仁,薛耀明,等.糖尿病肾病肾阴虚证DNA消减文库的构建[J].中医药学刊,2004(07).
[149]赵晓山,罗仁,张曦倩,等.肾阴虚证cDNA文库的构建[J].中国现代医学杂志,2007,17(3)：285-290.
[150]李玉萍,罗仁,赵晓山,等.慢性肾炎肾阴虚证cDNA消减文库的构建[J].上海中医药大学学报,2006,20(1)：57-60.
[151]李玉萍,罗仁,赵晓山,等.狼疮性肾炎肾阴虚证cDNA消减文库的构建[J].四川中医,2006,24(3)：22-24.
[152]代方国,赵晓山,罗仁,等.构建中国汉族人亚健康状态肾阴虚证的DNA消减文库[J].中国临床康复,2005(19).
[153]祁明浩,詹臻.基因芯片技术在中医证研究中的思考与应用[J].中医药学刊,2006(11).
[154]沈自尹.以药测证对肾虚证基因网络和信号转导的研究[J].中国中西医结合杂志,2005(12).
[155]沈自尹,陈瑜,黄建华,等.以药测证绘制肾虚证两大基因网络调控路线图谱[J].中国中西医结合杂志,2006(06).
[156]沈自尹,黄建华.EF调控老年大鼠淋巴细胞基因表达谱中凋亡相关信号分子表达的研究[J].中国免疫学杂志,2005(03).
[157]刘喜平.蛋白质组学与中医方证研究思考[J].中医杂志,2004,45(4)：247-248.
[158]孙晓敏.肾阴虚证的血浆蛋白组学初步研究[D].南方医科大学,2008.
[159]唐利华,卢德赵,沃兴德,等.肾上腺切除的肾阳虚大鼠肝组织蛋白质双向电泳图谱的建立与分析[J].浙江中医学院学报,2005,29(5)：51-54.
[160]中华中医药学会.亚健康中医临床指南[M].北京：中国中医药出版社,2006.2-3.
[161]沈自尹.中医虚证辨证参考标准[J].中西医结合杂志.1986：598.
[162]Reddi A H. Role of morphogenetic proteins in skeletal tissue engineering and regeneration[J]. Nat Biotechnol,1998,16(3):247-252.
[163]Colotta F, Re F, Polentarutti N, et al. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products[J]. Blood,1992,80(8):2012-2020.
[164]Teitelbaum S L, Ross F P. Genetic regulation of osteoclast development and function[J]. Nat Rev Genet,2003,4(8):638-649.
[165]Woo K M, Kim H M, Ko J S. Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-X(L)[J]. Exp Mol Med,2002,34(5):340-346.
[166]Owen T A, Smock S L, Prakash S, et al. Identification and characterization of the genes encoding human and mouse osteoactivin[J]. Crit Rev Eukaryot Gene Expr,2003,13(2-4):205-220.
[167]Abdelmagid S M, Barbe M F, Rico M C, et al. Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function[J]. Exp Cell Res,2008,314(13):2334-2351.
[168]Selim A A, Abdelmagid S M, Kanaan R A, et al. Anti-osteoactivin antibody inhibits osteoblast differentiation and function in vitro[J]. Crit Rev Eukaryot Gene Expr,2003,13(2-4):265-275.
[169]Furochi H, Tamura S, Mameoka M, et al. Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts[J]. FEBS Lett,2007,581(30):5743-5750.
[170]Ogawa T, Nikawa T, Furochi H, et al. Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice[J]. Am J Physiol Cell Physiol,2005,289(3):C697-C707.
[171]Lubberts E, Koenders M I, van den Berg W B. The role of T-cell interleukin-17 in conducting destructive arthritis:lessons from animal models[J]. Arthritis Res Ther,2005,7(1):29-37.
[172]王毅,邢国胜,于顺禄,等.IL—1β诱导软骨细胞培养金属蛋白酶/金属蛋白酶抑制剂水平及药物对其影响[J].中华风湿病学杂志,2003,7(12)：718-721.
[173]Aiuti A, Webb I J, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+progenitors to peripheral blood[J]. J Exp Med,1997,185(1):111-120.
[174]Bleul C C, Fuhlbrigge R C, Casasnovas J M, et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)[J]. J Exp Med,1996,184(3):1101-1109.
[175]Mohle R, Bautz F, Rafii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1[J]. Blood,1998,91(12):4523-4530.
[176]Zhang X F, Wang J F, Matczak E, et al. Janus kinase 2 is involved in stromal cell-derived factor-1 alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells[J]. Blood,2001,97(11):3342-3348.
[177]Yang D, Koupenova M, Mccrann D J, et al. The A2b adenosine receptor protects against vascular injury[J]. Proc Natl Acad Sci U S A,2008,105(2):792-796.
[178]Lataillade J J, Clay D, Dupuy C, et al. Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines:possible role in progenitor survival[J]. Blood,2000,95(3):756-768.
[179]Sempowski G D, Hale L P, Sundy J S, et al. Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy[J]. J Immunol,2000,164(4):2180-2187.
[180]Mukouyama Y, Hara T, Xu M, et al. In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region[J]. Immunity,1998,8(l):105-114.
[181]Tanaka M, Hirabayashi Y, Sekiguchi T, et al. Targeted disruption of oncostatin M receptor results in altered hematopoiesis[J]. Blood,2003,102(9):3154-3162.
[182]Yanai N, Obinata M. Oncostatin m regulates mesenchymal cell differentiation and enhances hematopoietic supportive activity of bone marrow stromal cell lines[J]. In Vitro Cell Dev Biol Anim,2001,37(10):698-704.
[183]Minehata K, Takeuchi M, Hirabayashi Y, et al. Oncostatin m maintains the hematopoietic microenvironment and retains hematopoietic progenitors in the bone marrow[J]. Int J Hematol,2006,84(4):319-327.
[184]Barreda D R, Hanington P C, Belosevic M. Regulation of myeloid development and function by colony stimulating factors[J]. Dev Comp Immunol,2004,28(5):509-554.
[185]Schneider-Brachert W, Tchikov V, Neumeyer J, et al. Compartmentalization of TNF receptor 1 signaling:internalized TNF receptosomes as death signaling vesicles[J], Immunity,2004,21 (3):415-428.
[186]Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes[J]. Cell,2003,114(2):181-190.
[187]Morgan M, Thorburn J, Pandolfi P P, et al. Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms[J]. J Cell Biol,2002,157(6):975-984.
[188]Bender L M, Morgan M J, Thomas L R, et al. The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm[J]. Cell Death Differ,2005,12(5):473-481.
[189]Comoglio P M, Trusolino L. Invasive growth:from development to metastasis[J]. J Clin Invest,2002,109(7):857-862.
[190]Glozak M A, Rogers M B. Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4[J]. Dev Biol,1996,179(2):458-470.
[191]Glozak M A, Rogers M B. BMP4- and RA-induced apoptosis is mediated through the activation of retinoic acid receptor alpha and gamma in P19 embryonal carcinoma cells[J]. Exp Cell Res,1998,242(1):165-173.
[192]Soda H, Raymond E, Sharma S, et al. Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units[J]. Anticancer Drugs,1998,9(4):327-331.
[193]Iantosca M R, Simon R H. Chronic subdural hematoma in adult and elderly patients[J]. Neurosurg Clin N Am,2000,11(3):447-454.
[194]Zuzarte-Luis V, Montero J A, Rodriguez-Leon J, et al. A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways[J]. Dev Biol,2004,272(1):39-52.
[195]Ro T B, Holt R U, Brenne A T, et al. Bone morphogenetic protein-5,-6 and -7 inhibit growth and induce apoptosis in human myeloma cells[J]. Oncogene,2004,23(17):3024-3032.
[196]Johnsen I K, Kappler R, Auernhammer C J, et al. Bone morphogenetic proteins 2 and 5 are down-regulated in adrenocortical carcinoma and modulate adrenal cell proliferation and steroidogenesis[J]. Cancer Res,2009,69(14):5784-5792.
[197]Byrne A T, Southgate J, Brison D R, et al. Effects of insulin-like growth factors Ⅰ and Ⅱ on tumour-necrosis-factor-alpha-induced apoptosis in early murine embryos[J]. Reprod Fertil Dev,2002,14(1-2):79-83.
[198]Petley T, Graff K, Jiang W, et al. Variation among cell types in the signaling pathways by which IGF-I stimulates specific cellular responses[J]. Horm Metab Res,1999,31(2-3):70-76.
[199]Abi-Younes S, Sauty A, Mach F, et al. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques[J]. Circ Res,2000,86(2):131-138.
[200]Zernecke A, Bot I, Djalali-Talab Y, et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis[J]. Circ Res,2008,102(2):209-217.
[201]Melchionna R, Porcelli D, Mangoni A, et al. Laminar shear stress inhibits CXCR4 expression on endothelial cells:functional consequences for atherogenesis[J]. FASEB J,2005,19(6):629-631.
[202]Qiao J H, Tripathi J, Mishra N K, et al. Role of macrophage colony-stimulating factor in atherosclerosis:studies of osteopetrotic mice[J]. Am J Pathol,1997,150(5):1687-1699.
[203]Schaub R G, Bree M P, Hayes L L, et al. Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol and carrageenan granuloma foam cell formation in Watanabe heritable hyperlipidemic rabbits[J]. Arterioscler Thromb,1994,14(1):70-76.
[204]Harrington L E, Hatton R D, Mangan P R, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol,2005,6(1 1):1123-1132.
[205]Park H, Li Z, Yang X O, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J]. Nat Immunol,2005,6(11):1133-1141.
[206]Ivanov 11, Mckenzie B S, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells[J]. Cell,2006,126(6):1121-1133.
[207]Kirkham B W, Lassere M N, Edmonds J P, et al. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis:a two-year prospective study (the DAMAGE study cohort)[J]. Arthritis Rheum,2006,54(4):1122-1131.
[208]Rohn T A, Jennings G T, Hernandez M, et al. Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis[J]. Eur J Immunol,2006,36(11):2857-2867.
[209]Wong C K, Ho C Y, Li E K, et al. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus[J]. Lupus,2000,9(8):589-593.
[210]Kurasawa K, Hirose K, Sano H, et al. Increased interleukin-17 production in patients with systemic sclerosis[J]. Arthritis Rheum,2000,43(11):2455-2463.
[211]Honorati M C, Neri S, Cattini L, et al. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts[J]. Osteoarthritis Cartilage,2006,14(4):345-352.
[212]Starnes T, Robertson M J, Sledge G, et al. Cutting edge:IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production[J]. J Immunol,2001,167(8):4137-4140.
[213]Liang S C, Long A J, Bennett F, et al. An IL-17F/A heterodimer protein is produced by mouse Thl7 cells and induces airway neutrophil recruitment[J]. J Immunol,2007,179(11):7791-7799.
[214]Ishigame H, Kakuta S, Nagai T, et al. Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses[J]. Immunity,2009,30(1):108-119.
[215]Oosterwegel M A, Greenwald R J, Mandelbrot D A, et al. CTLA-4 and T cell activation[J]. Curr Opin Immunol,1999,11(3):294-300.
[216]Stein J V, Soriano S F, M'Rini C, et al. CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway[J]. Blood,2003,101(1):38-44.
[217]Gunn M D, Tangemann K, Tam C, et al. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes[J]. Proc Natl Acad Sci U S A,1998,95(1):258-263.
[218]Jinquan T, Quan S, Jacobi H H, et al. CXC chemokine receptor 4 expression and stromal cell-derived factor-1alpha-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 and interleukin-10[J]. Immunology,2000,99(3):402-410.
[219]Nanki T, Hayashida K, El-Gabalawy H S, et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium[J]. J Immunol,2000,165(11):6590-6598.
[220]Nanki T, Lipsky P E. Cutting edge:stromal cell-derived factor-1 is a costimulator for CD4+ T cell activation[J]. J Immunol,2000,164(10):5010-5014.
[221]Dunussi-Joannopoulos K, Zuberek K, Runyon K, et al. Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1):local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses[J]. Blood,2002,100(5):1551-1558.
[222]Price T J, Louria M D, Candelario-Soto D, et al. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF:effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion[J]. BMC Neurosci,2005,6:4.
[223]Zhang Y H, Chi X X, Nicol G D. Brain-derived neurotrophic factor enhances the excitability of rat sensory neurons through activation of the p75 neurotrophin receptor and the sphingomyelin pathway[J]. J Physiol,2008,586(13):3113-3127.
[224]Pringle A K, Sundstrom L E, Wilde G J, et al. Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures[J]. Neurosci Lett,1996,211(3):203-206.
[225]Yamasaki Y, Shigeno T, Furukawa Y, et al. Reduction in brain-derived neurotrophic factor protein level in the hippocampal CA1 dendritic field precedes the delayed neuronal damage in the rat brain[J]. J Neurosci Res,1998,53(3):318-329.
[226]Li F, Chong Z Z, Maiese K. Winding through the WNT pathway during cellular development and demise[J]. Histol Histopathol,2006,21(1):103-124.
[227]Cao G, O'Brien C D, Zhou Z, et al. Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration[J]. Am J Physiol Cell Physiol,2002,282(5):C1181-C1190.
[228]Thompson R D, Wakelin M W, Larbi K Y, et al. Divergent effects of platelet-endothelial cell adhesion molecule-1 and beta 3 integrin blockade on leukocyte transmigration in vivo[J]. J Immunol,2000,165(1):426-434.
[229]Brown S, Heinisch I, Ross E, et al. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment[J]. Nature,2002,418(6894):200-203.
[230]Evans P C, Taylor E R, Kilshaw P J. Signaling through CD31 protects endothelial cells from apoptosis[J]. Transplantation,2001,71(3):457-460.
[231]Seifer D B, Feng B, Shelden R M. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles[J]. Am J Obstet Gynecol,2006,194(4):1129-1134,1134-1136.
[232]Seifer D B, Feng B, Shelden R M, et al. Brain-derived neurotrophic factor:a novel human ovarian follicular protein[J]. J Clin Endocrinol Metab,2002,87(2):655-659.
[233]Seifer D B, Lambert-Messerlian G, Schneyer A L. Ovarian brain-derived neurotrophic factor is present in follicular fluid from normally cycling women[J]. Fertil Steril,2003,79(2):451-452.
[234]Tsuchida K, Matsuzaki T, Yamakawa N, et al. Intracellular and extracellular control of activin function by novel regulatory molecules[J]. Mol Cell Endocrinol,2001,180(1-2):25-31.
[235]Sunder S, Lenton E A. Endocrinology of the peri-implantation period[J]. Baillieres Best Pract Res Clin Obstet Gynaecol,2000,14(5):789-800.
[236]Jones R L, Salamonsen L A, Zhao Y C, et al. Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization[J]. Mol Hum Reprod,2002,8(4):363-374.
[237]Seki T, Yun J, Oh S P. Arterial endothelium-specific activin receptor-like kinase 1 expression suggests its role in arterialization and vascular remodeling[J]. Circ Res,2003,93(7):682-689.
[238]Cole K E, Strick C A, Paradis T J, et al. Interferon-inducible T cell alpha chemoattractant (I-TAC):a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3[J]. J Exp Med,1998,187(12):2009-2021.
[239]吴学玲,赵云峰,钱桂生.脂多糖结合蛋白研究进展[J].国际呼吸杂志,2009,29(1)：39-43.
[240]Villarino A V, Larkin J R, Saris C J, et al. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation[J]. J Immunol,2005,174(12):7684-7691.
[241]Hibbert L, Pflanz S, De Waal M R, et al. IL-27 and IFN-alpha signal via Statl and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells[J]. J Interferon Cytokine Res,2003,23(9):513-522.
[242]Feng N, Lugli S M, Schnyder B, et al. The interleukin-4/interleukin-13 receptor of human synovial fibroblasts:overexpression of the nonsignaling interleukin-13 receptor alpha2[J]. Lab Invest,1998,78(5):591-602.
[243]Macdonald T T. Decoy receptor springs to life and eases fibrosis[J]. Nat Med,2006,12(1):13-14.
[244]Dangerfield J, Larbi K Y, Huang M T, et al. PECAM-1 (CD31) homophilic interaction up-regulates alpha6betal on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane[J]. J Exp Med,2002,196(9):1201-1211.
[245]Rieckmann T, Kotevic I, Trueb B. The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion[J]. Exp Cell Res,2008,314(5):1071-1081.
[246]Ohguchi M, Yamato K, Ishihara Y, et al. Activin A regulates the production of mature interleukin-1 beta and interleukin-1 receptor antagonist in human monocytic cells[J]. J Interferon Cytokine Res,1998,18(7):491-498.
[2]高博,尹桂山.Effect of tonifying kidney recipes on the protein kinase activity in hypothalamus of Kidney-yang-deficient rat[J].中国中医基础医学杂志,2000(01).
[3]曲耀华,刘彬,厉永强.补肾方剂对大鼠成骨样细胞增殖及相关酶类的影响[J].山东中医杂志,2003(07).
[4]高博,尹桂山.补肾药对肾阳虚大鼠下丘脑组织蛋白激酶活性的影响[Z].2000：6,30-33.
[5]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca-(2+)-Mg-(2+)-ATP酶活性影响的实验研究[J].中国骨质疏松杂志,1997(03).
[6]郑洪新,崔家鹏,刘景峰,等.肾虚骨质疏松症病理机制及补肾方药对其防治作用的实验研究[J].中国医药学报,1998(04).
[7]刘彬,皇甫超申,房娜.中药补肾方剂对大鼠骨肉瘤细胞增殖及相关酶活性的影响[J].第四军医大学学报,2006(03).
[8]沈自尹.衰老—生理性肾虚证的HPAT轴分子网络调控研究[J].中国中西医结合杂志,2004(09).
[9]胡聪,曾祥国.试论“肾充于脑”的物质基础[J].长春中医学院学报,1997,13(1)：1-3.
[10]江明,李庆阳,严桂珍.老年脾、肾虚与SOD、LPO关系探讨[J].长春中医学院学报,2000(04).
[11]江明,李庆阳,郑旭.老年脾、肾虚与SOD关系研究[J].安徽中医学院学报,1999(06).
[12]陈扬荣,江明,李庆阳.老年脾肾虚证LPO、SOD、血脂关系的探讨[J].中国中医基础医学杂志,2002(07).
[13]李庆阳,江明,严桂珍.老年脾肾虚证LPO、SOD、血脂及细胞免疫水平变化[J].福建中医学院学报,2001(03).
[14]刘华,周君富.老年人生理性肾虚潜在性血瘀证红细胞SODA与LPO的研究[J].现代中西医结合杂志,1997(02).
[15]姚明忠,赵伟康.A β诱导海马神经元调亡的机制及补肾方的调控作用[J].中国老年学杂志,2001,21(6)：450-452.
[16]陈洁文,王勇.巴戟素补肾健脑作用的神经活动基础[J].广州中医药大学学报,1999,16(4)：314-317.
[17]戴薇薇,金国琴,张学礼,等.补肾方药对衰老大鼠海马学习记忆相关基因BDNF及其受体TrkB mRNA表达的影响[J].中华中医药杂志,2008,23(4)：296-299.
[18]于文涛,张一听,吴中秋,等.补肾活血方对血管性痴呆小鼠行为学及脑海马自由基代谢的影响[J].中国老年学杂志,2009(12)：1478-1480.
[19]赵传康,李文.固真方对老年大鼠海马和下丘脑—垂体—肾上腺—胸腺轴作用的研究[J].中医杂志,1995,36(5)：300-302.
[20]冯新玲,周安方,田代志,等.恐伤孕鼠对其仔鼠大脑海马区细胞凋亡的影响[J].光明 中医,2008,23(8)：1079-1081.
[21]冯新玲,周安方,郑三一.恐伤孕鼠对其仔鼠大脑海马区乙酰胆碱代谢的影响[J].中医药信息,2009,26(3)：68-69.
[22]周慎,陈立峰,周重余,等.滋肾、温肾、活血三法对老龄小鼠海马区神经细胞密度的影响[J].中国老年学杂志,2006,26(3)：392-393.
[23]赵新永,金国琴,顾翠英,等.左归丸和右归丸对皮质酮所致大鼠海马神经细胞病理模型学习记忆相关信号转导分子mRNA表达的影响[J].中国老年学杂志,2010,30(5)：622-625.
[24]蒋淑君,崔存德,许兰芝.肾阳虚大鼠下丘脑-垂体-性腺轴钙调蛋白的基因表达及补肾中药的调整作用[J].中国临床康复,2004,8(24)：5056-5057.
[25]沈皓,蔡德培,陈伯英.补肾中药对下丘脑-垂体促性腺机能的影响[J].中西医结合学报,2004,2(1)：53-57.
[26]赵玉霞,孔令钧,等.补肾合剂对绝经后女性性激素及血脂代谢的影响[J].辽宁中医杂志,2001,28(9)：537-538.
[27]赖远征,冯冰虹,刘美珍,等.补肾活血方对更年期大鼠性激素的影响[J].辽宁中医杂志,2004,31(1)：78-79.
[28]李富宏,张西民,王桂花,等.补肾活血中药对女性激素的影响——附36例临床疗效观察[J].中华实用中西医杂志,2004,17(15)：2386-2387.
[29]张霞,吴连荣.从肾虚和性激素角度探讨老年糖尿病冠心病[J].辽宁中医杂志,2003,30(3)：207.
[30]毕会民,肖万泽.男性肾阳虚糖尿病性激素水平测定及临床意义[J].辽宁中医杂志,1997,24(10)：438.
[31]严炜.女性围绝经期综合征中医证型与性激素关系的研究[J].福建中医学院学报,2004,14(3)：1-4.
[32]郭瑞林,赵宁侠,等.吸毒对细胞免疫、自由基、性激素的影响及与中医肾虚的关系[J].第四军医大学学报,2002,23(14)：1312-1314.
[33]李灿东,高碧珍,兰启防,等.原发性不孕症中医辨证分型与性激素水平的相关性研究[J].中医杂志,2005,46(3)：216-218.
[34]王非,王平,郑杨,等.择时服用右归丸对肾阳虚大鼠性激素水平的影响[J].中国中医药科技,2006,13(6)：374.
[35]张树成,吴志奎.补肾生血和补肾调经方药促血管生成作用实验研究[J].中医杂志,2000,41(6)：369-370.
[36]张树成,沈明秀.补肾生血和补肾调经方药对老龄雌性金黄地鼠生殖器官组织形态的影响[J].中国民间疗法,1998,6(5)：56-57.
[37]马惠荣,杜惠兰,宋翠淼,等.补肾调经方对雄激素诱导无排卵大鼠氧化损伤、抗氧化能力及卵巢雌激素水平的影响[J].中药药理与临床,2004,20(5)：34-36.
[38]马惠荣,杜惠兰,杨秀芳,等.补肾调经方对雄激素致不孕大鼠卵巢组织抗氧化的实验研究[J].中华中医药杂志,2005,20(4)：252-253.
[39]杜惠兰,宋翠淼,马惠荣,等.补肾调经方对雄激素致不孕大鼠子宫一氧化氮、血清睾酮的影响[J].中成药,2007,29(2)：284-285.
[40]宋翠淼,杜惠兰,马爱蕊,等.补肾调经方对雄激素致不孕大鼠子宫转化生长因子β1 及其受体的影响[J].中成药,2007,29(5)：652-655.
[41]宋翠淼,杜惠兰,马惠荣,等.补肾调经方对雄激素致无排卵大鼠卵巢转化生长因子β1及其受体表达的影响[J].中国医科大学学报,2006,35(6)：600-602.
[42]王金萍.补肾调经方加减治疗崩漏80例临床观察[J].中外医疗,2009,28(34)：111.
[43]张树成,张志洲,等.补肾调经方调经促排卵健内膜作用的临床实验研究[J].中医药学刊,2002,20(6)：720-721.
[44]丛日杰.中西医结合治疗顽固性肾病水肿[J].内蒙古中医药,2010,29(3)：56.
[45]孙红,张燕.中西医结合治疗糖尿病肾病水肿疗效观察[J].中国中医药信息杂志,2008(S1).
[46]陈爱玲,李雷.金匮肾气汤加减治疗特发性水肿42例[J].河南中医,2008,28(6)：18-19.
[47]杨毅勇,桑志平,王娟娟.健脾补肾、补锌治疗不明原因水肿[J].中国中医药咨讯,2010(13)：282.
[48]覃正壮.防己黄芪汤治疗原发性肾病综合征水肿期疗效观察[J].吉林中医药,2010,30(7)：582-583.
[49]罗仁,成玉斌,等.“小四五汤”治疗糖尿肾病疗效与ACE基因相关性研究[J].上海中医药大学学报,2001,15(1)：24-26.
[50]薛耀明,成玉斌,周琳,等.Ⅰ型血管紧张素Ⅱ受体基因多态性与2型糖尿病肾病的相关研究[J].中华内科杂志,2001(3)：173-175.
[51]周琳,罗仁,等.ACE基因的插入／缺失多态性与2型糖尿病伴高血压的相互关系[J].第一军医大学学报,2002,22(9)：808-810.
[52]郭奕斌,吕英,蔡浩武,等.广东肾虚型哮喘病ACE基因的遗传多态性[J].中国优生与遗传杂志,2006,14(8)：20-22.
[53]成玉斌,罗仁,薛耀明,等.肾虚型DN与AGT及AGTIR基因多态性关系的研究[J].现代中西医结合杂志,2003,12(22)：2387-2388.
[54]成玉斌,罗仁,等.肾虚型糖尿病肾病与Ⅰ型血管紧张素Ⅱ受体基因多态性相关性研究[J].新中医,2003,35(1)：36-37.
[55]薛耀明,成玉斌,等.血管紧张素Ⅰ转换酶基因多态性与2型糖尿病肾病的易感性及病情发展的相关研[J].第一军医大学学报,2001,21(2)：85-87.
[56]高振,阿地力江·阿布力米提,哈木拉提·吾甫尔.哮喘的下丘脑-垂体-肾上腺轴紊乱及中医药介入的影响[J].实用医学杂志,2008,24(11)：1855-1856.
[57]解玉,杨子珍,柴柏春.上海市哮喘儿童与β2-肾上腺素能受体基因多态性的关系[J].实用儿科临床杂志,2008,23(4)：272-273.
[58]许建华,吴敦序,等.不同补肾法对哮喘大鼠肺组织β2肾上腺素能受体]mRNA的影响[J].上海中医药大学学报,2001,15(3)：38-40.
[59]包照日格,吴敦序.补肾健脾中药对哮喘模型大鼠肺组织β—肾上腺素能受体及cAMP的影响[J].中药新药与临床药理,2000,11(2)：98-100.
[60]石晓兰.β肾上腺素能受体和糖皮质激素受体与哮喘的关系及中医药对其作用的研究[J].河南中医,2005,25(4)：83-86.
[61]王明明,项晓人,徐建亚.补肺益肾方对幼龄哮喘豚鼠肺内嗜酸粒细胞凋亡和IL-5受体表达的影响[J].医学研究生学报,2010,23(7)：697-699.
[62]黄璧璇,张素玲,许新连.补肾纳气汤对儿童哮喘缓解期气道炎症影响的研究[J].现代医院,2009,9(7)：65-66.
[63]罗凤鸣,何成奇,等.加味肾气丸对支气管哮喘气道炎症抑制作用的临床研究[J].福建中医学院学报,2001,11(2)：13-14.
[64]张荣华,彭勇,杨丽,等.益骨胶囊对去卵巢骨质疏松大鼠血清PTH、KCT的影响[J].四川中医,2005,23(11)：37-38.
[65]陈津岩,李志强,何赞厚,等.右归丸对肾阳虚证大鼠激素水平变化的影响[J].中外健康文摘：医药月刊,2008,5(4)：44-46.
[66]张荣华,彭柯萍,朱晓峰,等.益骨胶囊含药血清对大鼠成骨细胞雌激素受体mRNA及其蛋白表达的影响[J].中国中西医结合杂志,2005,25(4)：333-337.
[67]林一峰,魏合伟,蔡桦,等.骨康及其含药血清中类性激素样物质含量的测定[J].中医药学刊,2003,21(5)：663-664.
[68]孔维萍,阎小萍.补肾强督法对强直性脊柱炎患者骨密度、骨代谢影响的临床研究[J].新中医,2008,40(10)：36-38.
[69]李楠,王和鸣,郭素华,等.巴戟天多糖及其水提取物对体外培养成骨细胞活性的影响[J].中国组织工程研究与临床康复,2007,11(23)：4570-4572.
[70]李楠,王和鸣,林旭,等.巴戟天对成骨细胞生物学特性影响的实验研究[J].中国医药学报,2004(12).
[71]李楠,王和鸣,郭素华,等.巴戟天多糖对体外培养成骨细胞核心结合因子α1mRNA表达的影响[J].中华中医药杂志,2007,22(8)：517-519.
[72]李楠,王和鸣,郭素华,等.巴戟天多糖含药血清对体外培养成骨细胞凋亡的保护作用观察[J].中国骨伤,2008,21(1)：39-41.
[73]陈亚琼,黄艳红,吴维光,等.补肾中药醇提活性部位对成骨细胞Cbfal基因表达的影响[J].武警医学院学报,2005(06).
[74]魏义勇,石印玉,詹红生,等.补肾中药对成骨细胞VDR, Cbfα 1mRNA表达的影响[J].中国骨伤,2006(11).
[75]魏义勇,石印玉,詹红生.补肾中药对成骨细胞维生素D受体与核心结合因子α1蛋白表达的影响[J].上海中医药杂志,2005(11).
[76]魏义勇,周琦,石印玉,等.补肾中药对老龄成骨细胞VDR基因表达的研究[J].中国中医骨伤科杂志,2006(04).
[77]尚德阳,郑洪新,宗志宏,等.补肾中药对肾虚骨质疏松症大鼠肾组织中Smurf2的mRNA和蛋白表达影响研究[J].中华中医药学刊,2008(08).
[78]魏义勇,石印玉,冯伟,等.补肾中药对增龄成骨细胞VDR蛋白表达的影响[J].中国骨质疏松杂志,2006(02).
[79]王巍巍,魏义勇,石印玉.补肾中药对增龄大鼠成骨细胞Cbfα_1表达的影响[J].中国中医药信息杂志,2007(11).
[80]李娟,吴贺勇,唐井钢.补肾中药骨灵丸对成骨细胞矿化功能及骨桥蛋白基因表达的影响[J].热带医学杂志,2006(01).
[81]夏远军,沈霖,谢晶,等.补肾中药密骨片对成骨细胞生长因子转化生长因子β1mRNA表达的影响(英文)[J].中国临床康复,2006(11).
[82]王玲巧,李恩.补肾方药对氢醌诱发的背毛脱色小鼠酶的活性影响[J].中国中西医结合杂志,1999,19(S1)：99-100.
[83]孙爱华,李津婴.补肾法为主治疗内耳疾病的思路与方法[J].中医杂志,1998,39(5)：305-307.
[84]孙爱华,李津婴.从缺铁肾虚大鼠耳蜗显微结构与生理功能变化探讨肾与耳联系的物质基础[J].中医研究,1993,6(3)：14-17.
[85]孙爱华,王正敏.肾主耳理论的生化物质基础：缺铁大鼠肾虚...[J].中医杂志,1991,32(3)：44-46.
[86]刘鲁明,鞠远秀,高季珍,等.试从钙磷代谢角度探讨肾虚耳鸣的物质基础——56例肾虚患者临床观察[J].中西医结合杂志,1986,6(9)：538-539.
[87]王彤.基于时藏理论的"肾主骨"与细胞信号转导相关性研究[D].北京：北京中医药大学,2007.
[88]刘晓燕,郭霞珍,等.中医“肾应冬”调控机制与下丘脑G蛋白关系的研究[J].中国医药学报,2002,17(11)：660-662.
[89]刘晓燕,郭霞珍,刘燕池,等.“肾应冬”与性腺轴相关性的研究[J].中国医药学报,2003,18(9)：522-524.
[90]郭霞珍."肾应冬"生理机制的研究[J].中华中医药杂志,2004(z1)：74-76.
[91]沈自尹.肾的研究(续集)[M].上海：上海科学技术出版社,1990.313.
[92]沈自尹.肾的研究进展与总结[J].中华中医药杂志,1988(02).
[93]方素钦,林炳辉,叶盈,等.中老年人肾虚证与性激素及免疫功能的研究[J].福建中医药,2002(02).
[94]田鄂华,俞金秀.肝郁脾虚证酶学指标的初步探讨[J].湖北中医杂志,1989(3)：43-44.
[95]宋春风.肾阳虚大鼠下丘脑-垂体-靶腺轴超微结构和Ca<\'2+>.CaM信号系统的改变及补肾中药的调整作用[D].河北医科大学,2000.
[96]宋春风,尹桂山,李恩,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴FOs蛋白表达的影响[J].中国中医基础医学杂志,2001,7(10)：36-37.
[97]宋春风,尹桂山,孙素菊,等.右归饮对肾阳虚大鼠下丘脑-垂体-肾上腺轴钙调素mRNA表达的影响[J].中国中医基础医学杂志,2001,7(3)：20-23.
[98]宋春风,尹桂山,赵建宏,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴CaMPKII的影响[J].中国中医基础医学杂志,2001,7(8)：45-47.
[99]宋春风,郑师陵,吕佩源,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴、血淋巴细胞Ca2+和血清钙的影响[J].中国中医基础医学杂志,2002,8(5)：34-36.
[100]郭凯,徐蓉,俞伟,等.金匮肾气丸对肾阳虚动物模型影响的拆方研究[J].中医药学报,2003,31(1)：20-21.
[101]金国琴,赵伟康.补肾药延缓老年大鼠下丘脑—垂体—甲状腺轴的功能退化[J].标记免疫分析与临床,1998,5(1)：32-35.
[102]青姚,张志哲.肾阳虚患者甲状腺激素水平变化及温补肾阳的疗效观察[J].广西中医学院学报,2001,4(4)：63-64.
[103]杨丹丹,詹臻.温肾补阳方对实验性免疫低下小鼠胸腺免疫细胞分化影响的实验研究[J].江苏中医药,2005,26(3)：51-53.
[104]徐卫东,陆平成.补肾复方对胸腺细胞增殖周期、胸腺一氧化氮及抗氧化作用的影响[J].浙江中医药大学学报,2007(6)：693-694.
[105]张玲娟,沈自尹.补肾益气法对淋巴细胞糖皮质激素受体老年性改变的影响[J].中西医结合杂志,1990,10(10)：583-585.
[106]詹秀琴.补肾方药对老年大鼠胸腺细胞糖皮质激素受体的作用研究[J].南京中医药大学学报,2000,16(3)：152-153.
[107]秦路平,石汉平.蛇床子香豆素对肾阳虚模型大鼠学习记忆和神经肽的影响[J].第二军医大学学报,1997,18(2)：147-149.
[108]陈小峰,王培训,李道中.肾虚患者的自然杀伤细胞活性研究[J].中国中西医结合杂志,1989(07).
[109]陈小峰,许少峰.肾虚患者的细胞因子研究[J].福建中医学院学报,2000,10(2)：12-13.
[110]陈小峰,许少锋.肾与白细胞介素的关系——附28例肾虚患者的临床研究[J].中国中医基础医学杂志,2000(12).
[111]陈瑜,沈自尹,郭为民.老年大鼠T细胞凋亡相关基因表达模式的研究[J].中国老年学杂志,2002(05).
[112]范国荣,王晓玲.老年人肾虚证的T细胞亚群及对免疫调控的影响[J].中国中西医结合杂志,1992,12(8)：478-479.
[113]华碧春,陈小峰,杜建,等.补肾B方对老龄SD大鼠细胞因子表达的调节作用[J].中华中医药学刊,2008(06).
[114]华碧春,陈小峰,郑良朴,等.补肾A方对老龄SD大鼠细胞因子表达的调节作用[J].光明中医,2008(07).
[115]江明,李奕棋,李庆阳.老年脾、肾虚与细胞免疫关系研究[J].中国医药学报,2000(05).
[116]李庆阳,郑家铿.老年肾虚与T细胞亚群关系[J].福建中医学院学报,2001(02).
[117]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探[J].福建医药杂志,2000(S1).
[118]沈自尹,郭为民,陈瑜.补肾方对老年人T细胞凋亡相关基因群转录的调控模式研究[J].中国老年学杂志,2002(04).
[119]宋淑霞,蔡月花,李杰,等.益气补肾方药对老年小鼠T细胞凋亡及凋亡相关基因表达的影响[J].中华老年医学杂志,2003(04).
[120]宋淑霞,冯旭,蔡月花,等.益气补肾药方对老龄小鼠T细胞中NF-κB活性的影响及作用机制[J].细胞与分子免疫学杂志,2004(02).
[121]宋淑霞,吕占军,等.益气补肾方药对肾虚小鼠细胞因子IL—2、IL—2及IL--12基因表达的影响[J].中国实验动物学报,2002,10(2)：101-104.
[122]宋淑霞,吕占军,刘福英.益气补肾方药对肾虚小鼠脾细胞CD40、CD40L表达的调节[J].中华老年医学杂志,2002(05).
[123]杨嘉珍.肾虚血瘀证与红细胞免疫的关系[J].湖北中医杂志,1996(03).
[124]张文彭,王巍,等.老年肾虚证血浆过氧化脂质高密度脂蛋白胆固醇及其亚组分水平变化[J].中医杂志,1989,30(2)：43-46.
[125]陈晏珍,江家贵,等.肾虚与超氧化物歧化酶关系初探[J].中医杂志,1989,30(4)：42-43.
[126]江明,李庆阳,郑旭.老年脾肾虚与LPO关系研究[J].陕西中医学院学报,1999(05).
[127]冯端浩,刘洪尊,等.脾虚和肾虚小鼠模型红细胞膜流动性的变化[J].广州中医药大学学报,2003,20(1)：21-24.
[128]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca-(2+)-Mg-(2+)-ATP酶活性影响的实验研究[J].中国骨质疏松杂志,1997(03).
[129]郭金瑞,严惠芳.慢性肾炎唾液Na+、K+红细胞变形能力改变与肾阴虚证相关性研究[J].中医药学刊,2003,21(11)：1900-1901.
[130]陈德珍,管学忠.脾肾阴虚证患者血清铜锌含量的变化[J].辽宁中医杂志,1999,26(7)：291.
[131]马威,管竞环.用血液微量元素观察右归丸治疗肾阳虚证的实验研究[J].微量元素与健康研究,1999,16(2)：39-42.
[132]马正立,施玉华.填精补肾中药对老年大鼠下丘脑—垂体—性腺—胸腺轴的形态学研究[J].中医杂志,1989,30(8)：45-48.
[133]周锦鹏,徐凤仙.补肾中药对老年大鼠胸腺作用的光镜和电镜观察[J].上海中医药杂志,1994(4)：43-45.
[134]高岗.肾虚证代谢组学及六味地黄汤的干预研究[D].第二军医大学,2009.
[135]魏敏.肾阴虚证和肾阳虚证基因表达谱的比较研究[D].南方医科大学,2009.
[136]成玉斌,罗仁,薛耀明,等.肾虚型DN与ACE基因多态性相关研究[J].中国中医基础医学杂志,2002(05).
[137]成玉斌,罗仁,薛耀明,等.肾虚型DN与AGT及AGT1R基因多态性关系的研究[J].现代中西医结合杂志,2003,12(22)：2387-2388.
[138]成玉斌,罗仁,薛耀明,等.肾虚型糖尿病肾病与Ⅰ型血管紧张素Ⅱ受体基因多态性相关性研究[J].新中医,2003(01).
[139]Lim C S, Kim Y S, Chae D W, et al. Association of C-509T and T869C polymorphisms of transforming growth factor-betal gene with susceptibility to and progression of IgA nephropathy.[J]. Clin Nephrol,2005,63(2):61-67.
[140]钟逸斐,陈以平,邓跃毅.增生为主IgA肾病阴虚证与TGF-β1基因启动子区C-509T的相关性研究[J].湖北中医学院学报,2008(02).
[141]Miyata T, Nangaku M, Suzuki D, et al. A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy.[J]. J Clin Invest,1998,102(4):828-836.
[142]钟逸斐,陈以平,邓跃毅,等Megsin基因E1-5’UTR区A267G与免疫球蛋白A型肾病阴虚证的相关性[J].中西医结合学报,2008,6(5)：463-467.
[143]杨进,郭聂涛,李燕林,等.原发性肾病综合征中医辨证分型与红细胞CRl密度相关基因及数量表达和黏附活性的相关性[J].中国中西医结合肾病杂志,2005,6(3)：167-168.
[144]温成平,谢志军,宋平,等.系统性红斑狼疮中医证型与人类白细胞Ⅱ类抗原DR基因表达关系的研究[J].中国中西医结合杂志,2008(06).
[145]郑平东,肖黎,何立群,等.补肾方式经对IgA肾病肾虚证人群bcl—2基因表达变化的影响[J].中华国际医学杂志,2003,3(3)：210-212.
[146]孙伟正,赵淑英,等.慢性再生障碍性贫血中医辨证与HLA基因相关性研究[J].中国医药学报,2002,17(3)：167-169.
[147]孙伟正,杨东光,刚宏林.慢性再生障碍性贫血中医辨证分型与MHC—DRB1*等位 基因的相关性研究[J].中医杂志,2004,45(6)：450-452.
[148]赵晓山,罗仁,薛耀明,等.糖尿病肾病肾阴虚证DNA消减文库的构建[J].中医药学刊,2004(07).
[149]赵晓山,罗仁,张曦倩,等.肾阴虚证cDNA文库的构建[J].中国现代医学杂志,2007,17(3)：285-290.
[150]李玉萍,罗仁,赵晓山,等.慢性肾炎肾阴虚证cDNA消减文库的构建[J].上海中医药大学学报,2006,20(1)：57-60.
[151]李玉萍,罗仁,赵晓山,等.狼疮性肾炎肾阴虚证cDNA消减文库的构建[J].四川中医,2006,24(3)：22-24.
[152]代方国,赵晓山,罗仁,等.构建中国汉族人亚健康状态肾阴虚证的DNA消减文库[J].中国临床康复,2005(19).
[153]祁明浩,詹臻.基因芯片技术在中医证研究中的思考与应用[J].中医药学刊,2006(11).
[154]沈自尹.以药测证对肾虚证基因网络和信号转导的研究[J].中国中西医结合杂志,2005(12).
[155]沈自尹,陈瑜,黄建华,等.以药测证绘制肾虚证两大基因网络调控路线图谱[J].中国中西医结合杂志,2006(06).
[156]沈自尹,黄建华.EF调控老年大鼠淋巴细胞基因表达谱中凋亡相关信号分子表达的研究[J].中国免疫学杂志,2005(03).
[157]刘喜平.蛋白质组学与中医方证研究思考[J].中医杂志,2004,45(4)：247-248.
[158]孙晓敏.肾阴虚证的血浆蛋白组学初步研究[D].南方医科大学,2008.
[159]唐利华,卢德赵,沃兴德,等.肾上腺切除的肾阳虚大鼠肝组织蛋白质双向电泳图谱的建立与分析[J].浙江中医学院学报,2005,29(5)：51-54.
[160]中华中医药学会.亚健康中医临床指南[M].北京：中国中医药出版社,2006.2-3.
[161]沈自尹.中医虚证辨证参考标准[J].中西医结合杂志.1986：598.
[162]Reddi A H. Role of morphogenetic proteins in skeletal tissue engineering and regeneration[J]. Nat Biotechnol,1998,16(3):247-252.
[163]Colotta F, Re F, Polentarutti N, et al. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products[J]. Blood,1992,80(8):2012-2020.
[164]Teitelbaum S L, Ross F P. Genetic regulation of osteoclast development and function[J]. Nat Rev Genet,2003,4(8):638-649.
[165]Woo K M, Kim H M, Ko J S. Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-X(L)[J]. Exp Mol Med,2002,34(5):340-346.
[166]Owen T A, Smock S L, Prakash S, et al. Identification and characterization of the genes encoding human and mouse osteoactivin[J]. Crit Rev Eukaryot Gene Expr,2003,13(2-4):205-220.
[167]Abdelmagid S M, Barbe M F, Rico M C, et al. Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function[J]. Exp Cell Res,2008,314(13):2334-2351.
[168]Selim A A, Abdelmagid S M, Kanaan R A, et al. Anti-osteoactivin antibody inhibits osteoblast differentiation and function in vitro[J]. Crit Rev Eukaryot Gene Expr,2003,13(2-4):265-275.
[169]Furochi H, Tamura S, Mameoka M, et al. Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts[J]. FEBS Lett,2007,581(30):5743-5750.
[170]Ogawa T, Nikawa T, Furochi H, et al. Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice[J]. Am J Physiol Cell Physiol,2005,289(3):C697-C707.
[171]Lubberts E, Koenders M I, van den Berg W B. The role of T-cell interleukin-17 in conducting destructive arthritis:lessons from animal models[J]. Arthritis Res Ther,2005,7(1):29-37.
[172]王毅,邢国胜,于顺禄,等.IL—1β诱导软骨细胞培养金属蛋白酶/金属蛋白酶抑制剂水平及药物对其影响[J].中华风湿病学杂志,2003,7(12)：718-721.
[173]Aiuti A, Webb I J, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+progenitors to peripheral blood[J]. J Exp Med,1997,185(1):111-120.
[174]Bleul C C, Fuhlbrigge R C, Casasnovas J M, et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)[J]. J Exp Med,1996,184(3):1101-1109.
[175]Mohle R, Bautz F, Rafii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1[J]. Blood,1998,91(12):4523-4530.
[176]Zhang X F, Wang J F, Matczak E, et al. Janus kinase 2 is involved in stromal cell-derived factor-1 alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells[J]. Blood,2001,97(11):3342-3348.
[177]Yang D, Koupenova M, Mccrann D J, et al. The A2b adenosine receptor protects against vascular injury[J]. Proc Natl Acad Sci U S A,2008,105(2):792-796.
[178]Lataillade J J, Clay D, Dupuy C, et al. Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines:possible role in progenitor survival[J]. Blood,2000,95(3):756-768.
[179]Sempowski G D, Hale L P, Sundy J S, et al. Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy[J]. J Immunol,2000,164(4):2180-2187.
[180]Mukouyama Y, Hara T, Xu M, et al. In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region[J]. Immunity,1998,8(l):105-114.
[181]Tanaka M, Hirabayashi Y, Sekiguchi T, et al. Targeted disruption of oncostatin M receptor results in altered hematopoiesis[J]. Blood,2003,102(9):3154-3162.
[182]Yanai N, Obinata M. Oncostatin m regulates mesenchymal cell differentiation and enhances hematopoietic supportive activity of bone marrow stromal cell lines[J]. In Vitro Cell Dev Biol Anim,2001,37(10):698-704.
[183]Minehata K, Takeuchi M, Hirabayashi Y, et al. Oncostatin m maintains the hematopoietic microenvironment and retains hematopoietic progenitors in the bone marrow[J]. Int J Hematol,2006,84(4):319-327.
[184]Barreda D R, Hanington P C, Belosevic M. Regulation of myeloid development and function by colony stimulating factors[J]. Dev Comp Immunol,2004,28(5):509-554.
[185]Schneider-Brachert W, Tchikov V, Neumeyer J, et al. Compartmentalization of TNF receptor 1 signaling:internalized TNF receptosomes as death signaling vesicles[J], Immunity,2004,21 (3):415-428.
[186]Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes[J]. Cell,2003,114(2):181-190.
[187]Morgan M, Thorburn J, Pandolfi P P, et al. Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms[J]. J Cell Biol,2002,157(6):975-984.
[188]Bender L M, Morgan M J, Thomas L R, et al. The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm[J]. Cell Death Differ,2005,12(5):473-481.
[189]Comoglio P M, Trusolino L. Invasive growth:from development to metastasis[J]. J Clin Invest,2002,109(7):857-862.
[190]Glozak M A, Rogers M B. Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4[J]. Dev Biol,1996,179(2):458-470.
[191]Glozak M A, Rogers M B. BMP4- and RA-induced apoptosis is mediated through the activation of retinoic acid receptor alpha and gamma in P19 embryonal carcinoma cells[J]. Exp Cell Res,1998,242(1):165-173.
[192]Soda H, Raymond E, Sharma S, et al. Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units[J]. Anticancer Drugs,1998,9(4):327-331.
[193]Iantosca M R, Simon R H. Chronic subdural hematoma in adult and elderly patients[J]. Neurosurg Clin N Am,2000,11(3):447-454.
[194]Zuzarte-Luis V, Montero J A, Rodriguez-Leon J, et al. A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways[J]. Dev Biol,2004,272(1):39-52.
[195]Ro T B, Holt R U, Brenne A T, et al. Bone morphogenetic protein-5,-6 and -7 inhibit growth and induce apoptosis in human myeloma cells[J]. Oncogene,2004,23(17):3024-3032.
[196]Johnsen I K, Kappler R, Auernhammer C J, et al. Bone morphogenetic proteins 2 and 5 are down-regulated in adrenocortical carcinoma and modulate adrenal cell proliferation and steroidogenesis[J]. Cancer Res,2009,69(14):5784-5792.
[197]Byrne A T, Southgate J, Brison D R, et al. Effects of insulin-like growth factors Ⅰ and Ⅱ on tumour-necrosis-factor-alpha-induced apoptosis in early murine embryos[J]. Reprod Fertil Dev,2002,14(1-2):79-83.
[198]Petley T, Graff K, Jiang W, et al. Variation among cell types in the signaling pathways by which IGF-I stimulates specific cellular responses[J]. Horm Metab Res,1999,31(2-3):70-76.
[199]Abi-Younes S, Sauty A, Mach F, et al. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques[J]. Circ Res,2000,86(2):131-138.
[200]Zernecke A, Bot I, Djalali-Talab Y, et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis[J]. Circ Res,2008,102(2):209-217.
[201]Melchionna R, Porcelli D, Mangoni A, et al. Laminar shear stress inhibits CXCR4 expression on endothelial cells:functional consequences for atherogenesis[J]. FASEB J,2005,19(6):629-631.
[202]Qiao J H, Tripathi J, Mishra N K, et al. Role of macrophage colony-stimulating factor in atherosclerosis:studies of osteopetrotic mice[J]. Am J Pathol,1997,150(5):1687-1699.
[203]Schaub R G, Bree M P, Hayes L L, et al. Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol and carrageenan granuloma foam cell formation in Watanabe heritable hyperlipidemic rabbits[J]. Arterioscler Thromb,1994,14(1):70-76.
[204]Harrington L E, Hatton R D, Mangan P R, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol,2005,6(1 1):1123-1132.
[205]Park H, Li Z, Yang X O, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J]. Nat Immunol,2005,6(11):1133-1141.
[206]Ivanov 11, Mckenzie B S, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells[J]. Cell,2006,126(6):1121-1133.
[207]Kirkham B W, Lassere M N, Edmonds J P, et al. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis:a two-year prospective study (the DAMAGE study cohort)[J]. Arthritis Rheum,2006,54(4):1122-1131.
[208]Rohn T A, Jennings G T, Hernandez M, et al. Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis[J]. Eur J Immunol,2006,36(11):2857-2867.
[209]Wong C K, Ho C Y, Li E K, et al. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus[J]. Lupus,2000,9(8):589-593.
[210]Kurasawa K, Hirose K, Sano H, et al. Increased interleukin-17 production in patients with systemic sclerosis[J]. Arthritis Rheum,2000,43(11):2455-2463.
[211]Honorati M C, Neri S, Cattini L, et al. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts[J]. Osteoarthritis Cartilage,2006,14(4):345-352.
[212]Starnes T, Robertson M J, Sledge G, et al. Cutting edge:IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production[J]. J Immunol,2001,167(8):4137-4140.
[213]Liang S C, Long A J, Bennett F, et al. An IL-17F/A heterodimer protein is produced by mouse Thl7 cells and induces airway neutrophil recruitment[J]. J Immunol,2007,179(11):7791-7799.
[214]Ishigame H, Kakuta S, Nagai T, et al. Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses[J]. Immunity,2009,30(1):108-119.
[215]Oosterwegel M A, Greenwald R J, Mandelbrot D A, et al. CTLA-4 and T cell activation[J]. Curr Opin Immunol,1999,11(3):294-300.
[216]Stein J V, Soriano S F, M'Rini C, et al. CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway[J]. Blood,2003,101(1):38-44.
[217]Gunn M D, Tangemann K, Tam C, et al. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes[J]. Proc Natl Acad Sci U S A,1998,95(1):258-263.
[218]Jinquan T, Quan S, Jacobi H H, et al. CXC chemokine receptor 4 expression and stromal cell-derived factor-1alpha-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 and interleukin-10[J]. Immunology,2000,99(3):402-410.
[219]Nanki T, Hayashida K, El-Gabalawy H S, et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium[J]. J Immunol,2000,165(11):6590-6598.
[220]Nanki T, Lipsky P E. Cutting edge:stromal cell-derived factor-1 is a costimulator for CD4+ T cell activation[J]. J Immunol,2000,164(10):5010-5014.
[221]Dunussi-Joannopoulos K, Zuberek K, Runyon K, et al. Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1):local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses[J]. Blood,2002,100(5):1551-1558.
[222]Price T J, Louria M D, Candelario-Soto D, et al. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF:effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion[J]. BMC Neurosci,2005,6:4.
[223]Zhang Y H, Chi X X, Nicol G D. Brain-derived neurotrophic factor enhances the excitability of rat sensory neurons through activation of the p75 neurotrophin receptor and the sphingomyelin pathway[J]. J Physiol,2008,586(13):3113-3127.
[224]Pringle A K, Sundstrom L E, Wilde G J, et al. Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures[J]. Neurosci Lett,1996,211(3):203-206.
[225]Yamasaki Y, Shigeno T, Furukawa Y, et al. Reduction in brain-derived neurotrophic factor protein level in the hippocampal CA1 dendritic field precedes the delayed neuronal damage in the rat brain[J]. J Neurosci Res,1998,53(3):318-329.
[226]Li F, Chong Z Z, Maiese K. Winding through the WNT pathway during cellular development and demise[J]. Histol Histopathol,2006,21(1):103-124.
[227]Cao G, O'Brien C D, Zhou Z, et al. Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration[J]. Am J Physiol Cell Physiol,2002,282(5):C1181-C1190.
[228]Thompson R D, Wakelin M W, Larbi K Y, et al. Divergent effects of platelet-endothelial cell adhesion molecule-1 and beta 3 integrin blockade on leukocyte transmigration in vivo[J]. J Immunol,2000,165(1):426-434.
[229]Brown S, Heinisch I, Ross E, et al. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment[J]. Nature,2002,418(6894):200-203.
[230]Evans P C, Taylor E R, Kilshaw P J. Signaling through CD31 protects endothelial cells from apoptosis[J]. Transplantation,2001,71(3):457-460.
[231]Seifer D B, Feng B, Shelden R M. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles[J]. Am J Obstet Gynecol,2006,194(4):1129-1134,1134-1136.
[232]Seifer D B, Feng B, Shelden R M, et al. Brain-derived neurotrophic factor:a novel human ovarian follicular protein[J]. J Clin Endocrinol Metab,2002,87(2):655-659.
[233]Seifer D B, Lambert-Messerlian G, Schneyer A L. Ovarian brain-derived neurotrophic factor is present in follicular fluid from normally cycling women[J]. Fertil Steril,2003,79(2):451-452.
[234]Tsuchida K, Matsuzaki T, Yamakawa N, et al. Intracellular and extracellular control of activin function by novel regulatory molecules[J]. Mol Cell Endocrinol,2001,180(1-2):25-31.
[235]Sunder S, Lenton E A. Endocrinology of the peri-implantation period[J]. Baillieres Best Pract Res Clin Obstet Gynaecol,2000,14(5):789-800.
[236]Jones R L, Salamonsen L A, Zhao Y C, et al. Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization[J]. Mol Hum Reprod,2002,8(4):363-374.
[237]Seki T, Yun J, Oh S P. Arterial endothelium-specific activin receptor-like kinase 1 expression suggests its role in arterialization and vascular remodeling[J]. Circ Res,2003,93(7):682-689.
[238]Cole K E, Strick C A, Paradis T J, et al. Interferon-inducible T cell alpha chemoattractant (I-TAC):a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3[J]. J Exp Med,1998,187(12):2009-2021.
[239]吴学玲,赵云峰,钱桂生.脂多糖结合蛋白研究进展[J].国际呼吸杂志,2009,29(1)：39-43.
[240]Villarino A V, Larkin J R, Saris C J, et al. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation[J]. J Immunol,2005,174(12):7684-7691.
[241]Hibbert L, Pflanz S, De Waal M R, et al. IL-27 and IFN-alpha signal via Statl and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells[J]. J Interferon Cytokine Res,2003,23(9):513-522.
[242]Feng N, Lugli S M, Schnyder B, et al. The interleukin-4/interleukin-13 receptor of human synovial fibroblasts:overexpression of the nonsignaling interleukin-13 receptor alpha2[J]. Lab Invest,1998,78(5):591-602.
[243]Macdonald T T. Decoy receptor springs to life and eases fibrosis[J]. Nat Med,2006,12(1):13-14.
[244]Dangerfield J, Larbi K Y, Huang M T, et al. PECAM-1 (CD31) homophilic interaction up-regulates alpha6betal on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane[J]. J Exp Med,2002,196(9):1201-1211.
[245]Rieckmann T, Kotevic I, Trueb B. The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion[J]. Exp Cell Res,2008,314(5):1071-1081.
[246]Ohguchi M, Yamato K, Ishihara Y, et al. Activin A regulates the production of mature interleukin-1 beta and interleukin-1 receptor antagonist in human monocytic cells[J]. J Interferon Cytokine Res,1998,18(7):491-498.